Immunomodulation by thalidomide: Systematic review of the literature and of unpublished observations

Journal of Inflammation

Volumn 46, Issue 4, 1995, Pages 177-211

  Zwingenberger, K ^a  

^a GRÜNENTHAL GMBH   (Germany)

Author keywords

adhesion; cytokines; dermatology; mycobacteria; vasculitis

Indexed keywords

ANTIINFLAMMATORY AGENT; CORTICOSTEROID; CYCLOSPORIN A; CYTOKINE; IMMUNOMODULATING AGENT; MEMBRANE ANTIGEN; NONSTEROID ANTIINFLAMMATORY AGENT; PENTOXIFYLLINE; SEDATIVE AGENT; THALIDOMIDE; TRANSCRIPTION FACTOR; TUMOR NECROSIS FACTOR ALPHA;

ANGIOGENESIS; ANTIGEN EXPRESSION; ARTHRITIS; AUTOIMMUNITY; B LYMPHOCYTE; CELL PROLIFERATION; DRUG ACTIVITY; DRUG THERAPY; HUMAN; IMMUNOMODULATION; INFLAMMATION; LEUKOCYTE MIGRATION; MYCOBACTERIOSIS; NATURAL KILLER CELL; NONHUMAN; PHAGOCYTOSIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; TRANSPLANTATION; VASCULITIS;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; ANTI-INFLAMMATORY AGENTS; CHEMISTRY, PHYSICAL; CYTOKINES; HUMANS; HYPNOTICS AND SEDATIVES; LEUKOCYTES; MYCOBACTERIUM INFECTIONS; THALIDOMIDE; VASCULITIS;

EID: 0029548149     PISSN: 10787852     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (216)

1. Keller H, cited in Wenzel D, Wenzel KH (eds): "Der Contergan-Prozess, " vol. 2. Berlin: Wissenschaft und Forschung GmbH, 1968, pp 56-70.
2. Florence AL: Is thalidomide to blame? Br Med J (31 Dec): 1954, 1960.
3. Schröder JM, Gibbels E: Marklose Nervenfasern im Senium und im Spaetstadium der Thalidomid-Polyneuropathie: quantitative-elektronenmikroskopische Untersuchungen. Acta Neuropathol 39:271-280, 1977.
4. Lenz W: A short history of thalidomide embryopathy. Teratology 38:203-215, 1988.
5. Wiedemann HR: Hinweis auf eine derzeitige Häufung hypo- und aplastischer Fehlbildungen der Gliedmassen. Med Welt 37:1863, 1961.
6. McBride WG: Thalidomide and congenital abnormalities. Lancet (16 Dec):1358, 1961.
7. Somers GF: Pharmacological properties of thalidomide (alpha-phthalimido glutarimide), a new sedative hypnotic drug. Br J Pharmacol 15:111-116, 1960.
8. Miller JM, Ginsberg M, McElfatrick GC, Shonberg IL: The anti-inflammatory effect and the analgetic property of Thalidomide-268. Antibiot Med Clin Ther 7:743-746, 1960.
9. Ridley DS, Jopling WH: A classification of leprosy for research purposes. Lepr Rev 33:119-128, 1962.
10. Job CK, Jacobson RR, Hastings RC: Simultaneous upgrading reaction and erythema nodosum leprosum in a patient with lepromatous leprosy. Int J Lepr 56:437442, 1988.
11. Sheskin J: Thalidomide in the treatment of lepra reactions. Clin Pharmacol Ther 6:303-306, 1965.
12. Sheskin J: The treatment of lepra reaction in lepromatous leprosy. Int J Dermatol 19:318-322, 1980.
13. Hellmann K, Duke DI, Tucker DF: Prolongation of skin homograft survival by thalidomide. Br Med J (18 Sep):687-689, 1965.
14. Turk JL, Hellmann K, Duke DI: Effect of thalidomide on the immunological response in local lymph nodes after a skin homograft. Lancet (7447):1134-1136, 1966.
15. Vogelsang GB, Hess AD, Gordon G, Santos GW: Treatment and prevention of acute graft-versus-host disease with thalidomide in a rat model. Transplantation 41:644-647, 1986.
16. Field EO, Gibbs JE, Tucker DF, Hellmann K: Effect of thalidomide on the graft versus host reaction. Nature 211:1308-1310, 1966.
17. Roath S, Elves MW, Israels MCC: Effect of thalidomide on leucocyte cultures. Lancet (20 Oct):812-813, 1962.
18. Desowitz RS: "The Thorn in the Starfish." New York: W.W. Norton, 1987.
19. Playfair JHL, Leuchars E, Davies AJS: Effect of thalidomide on skin-graft survival. Lancet (4 M ay): 1003-1004, 1963.
20. Günzler V, Hanauske-Abel HM, Tschank G, SchulteWissermann H: Immunological effects of thalidomide: inactivity of the drug and several of its hydrolysis products in mononucleocyte proliferation tests. ArzneimForsch/Drug Res 36:1138-1141, 1986.
21. McHugh SM, Rifkin IR, Deighton J, Wilson AB, Lachmann PJ, Ewan PW, Lockwood CM: The immunosuppressive drug thalidomide induces T helper cell type 2 (Th2) and concomitantly inhibits Thl cytokine production in mitogen- and antigen-stimulated human peripheral blood mononuclear cell cultures. Clin Exp Immunol 99:160-167, 1995.
22. Zhu J, Bai X, Mix E, van der Meide P, Link H: Thalidomide suppresses T and B cell responses to myelin antigen in experimental allergic neuritis. Clin Neuropharm, in press.
23. Jacobson RR: Treatment of leprosy. In Hastings RC (ed): "Leprosy." Edinburgh: Churchill Livingstone, 1994, pp 317-349.
24. Cornea P, Vladutiu A, Marcovici G: The immunosuppressive effect of thalidomide in experimental tuberculosis in guinea-pigs. Tubercle 48:51-53, 1967.
25. Moreira A, Wang J, Tsenova L, North R, Kaplan G: The effect of thalidomide on the cellular immune response to mycobacteria infection in mice. J Cell Biochem Suppl (19B):88, 1995.
26. Neubert R: Thalidomide. In Spencer PS, Schaumburg HS (eds): "Experimental and Clinical Neurotoxicology, " 2nd ed. Oxford University Press, 1996.
27. Neubert R, Neubert D. Peculiarities and possible mode of the actions of thalidomide. In Kavlock, Daston (eds): "Drug Toxicity in Embryonic Development." Handbook of Experimental Pharmacology 124. Heidelberg: Springer Verlag, 1996 pp. 41-119.
28. Ochonisky S, Revuz J: Thalidomide use in dermatology. Eur J Dermatol 4:9-15, 1994.
29. Gardner-Medwin JM: Thalidomide in autoimmune conditions. Exp Opin Invest Drugs, 5:829-841, 1996.
30. Winter W, Frankus E: Thalidomide enantiomers. Lancet 339:365, 1992.
31. Eriksson T, Björkman S, Roth B, Fyge A, Höglund P: Stereospecific determination, chiral inversion in vitro and pharmacokinetics in humans of the enantiomers of thalidomide (Kinetics of the enantiomers of thalidomide). Chirality 7:44-52, 1995.
32. Wnendt S, Finkam M, Winter W, Raabe G, Ossig J, Zwingenberger K: Enantiospecific inhibition of TNFot release by thalidomide and thalidomide analogues. Chirality, in press.
33. Hague D, Smith RL: Enigmatic properties of (+/-)thalidomide: An example of a stable racemic compound. Br J Clin Pharmacol 26:623P, 1988.
34. Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G: Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med 173:699-703, 1991.
35. Koch H: Die Arenoxid-Hypothese der Thalidomid-Wirkung. Überlegungen zum molekularen Wirkungsmechanismus des klassischen Teratogens. Sci Pharm 49:6799, 1981.
36. Atra E, Sato El: Treatment of the cutaneous lesions of systemic lupus erythematosus with thalidomide. Clin Exp Rheumatol 11:487-493, 1993.
37. Koransky W, Ullberg S: Autoradiographic investigations of C-labelled thalidomide and glutethimide in pregnant mice. Proc Soc Exp Biol Med 116:512-516, 1964.
38. Tanaka A, Hasegawa A, Urakubo G: Metabolic fate of thalidomide in rats. Chem Pharm Bull 13:1263-1265, 1965.
39. MacKenzie RD, McGrath WR: Absorption of thalidomide in the rat. Proc Soc Exp Biol Med 109:511-515, 1962.
40. Schumacher H, Smith RL, Williams RT: The metabolism of thalidomide: The fate of thalidomide and some of its hydrolysis products in various species. Br J Pharmacol 25:338-351, 1965.
41. Beckmann R: Ueber das Verhalten von Thalidomid im Organismus-1. Mitteilung: Resorption, Verteilung im Gewebe und Ausscheidung von N-Phthalyl-glutaminsäureimid-14C (Thalidomid-14C). Arzneim-Forsch/Drug Res 12:1095-1098, 1962.
42. Beckmann R: Ueber das Verhalten von Thalidomid im Organismus-2. Mitteilung: Biologischer Abbau von NPhthalyl-D, L-glutaminsäureimid-14C (Thalidomid-'4C). Arzneim-Forsch/Drug Res 13:185-191, 1963.
43. Förster M, Neubert R: Lack of effects on fetal thymus and lymphocyte development in marmoset fetuses and newborns following treatment with thalidomide. Teratology 51:23A-24A, 1995.
44. Maurice PDL, Barkley ASJ, Allen BR: The effect of thalidomide on arachidonic acid metabolism in human polymorphonuclear leukocytes and platelets. Br J Dermatol 115:677-680, 1986.
45. Hensby CN, Maloubier A, Civier A, Shroot B, Ortonne JP: A model for studying the anti-prostaglandin activity of drugs in human skin. Br J Dermatol 111(Suppl 271:147-151, 1984.
46. Roath S, Elves MW, Israels MCG: Effects of thalidomide and its derivatives on human leucocytes cultured in vitro. Lancet (2 Feb):249-250, 1963.
47. Vogelsang GB, Hess AD, Gordon G, Brundrette R, Santos GW: Thalidomide induction of bone marrow transplantation tolerance. Transplant Proc 19:2658-2661, 1987.
48. Gasparini C, Bersi M, Romito S: The effects of N-phthalyl-glutamic acid imide (thalidomide). Note II: Cytostatic action on medullary cells and peripheral blood lymphocytes in culture. Arch Sci Med 128:89-90, 1971.
49. Lindahl-Kiessling K, Boeck JA: Effects of thalidomide on human leucocyte cultures. Lancet (24 Aug):405, 1963.
50. Ogilvie JW, Kantor FS: The effect of thalidomide on the immune response. Fed Proc 27:494, 1968.
51. Coulson AS, Summers LJ, Lindahl-Kiessling K, Tucker D, Hellmann K: The effect of two soluble thalidomide derivatives on lymphocyte stimulation. Clin Exp Immunol 7:241-247, 1970.
52. Tramontana J, Utaipat U, Molloy A, Akrasewi P, Burroughs M, Makonkawkeyoon S, Johnson B, Kaplan G: Thalidomide treatment of patients with pulmonary tu-berculosis reduces TNF-alpha production and enhances weight gain. Mol Med 1:384-397, 1995.
53. Schlegel PG, Fernandez LP, Baker J, Chen Y, Chao NJ: Thalidomide does not modulate the IL-2 response of activated Jurkat cells as measured by beta-gal-activity and by IL-2 production. Blood 84(10 Suppl 1}:431a, 1994.
54. Fernandez LP, Schlegel PG, Baker J, Chen YF, Chao NJ: Does thalidomide affect IL-2 response and production? Exp Hematol 23:978-985, 1995.
55. Shannon EJ, Sandoval F: Thalidomide increases the synthesis of IL-2 in cultures of human mononuclear cells stimulated with Concanavalin-A, staphylococcal enterotoxin A, and purified protein derivative. Immunopharmacology 31:109-116, 1995.
56. Östraat Ö, Riesbeck K, Qi Z, Eriksson T, Schatz H, Ekberg H: Thalidomide prolonged graft survival in a rat cardiac transplant model, but had no inhibitory effect on lymphocyte function in vitro. Transplant Immunol, in press.
57. Schneider J, Bruckmann W, Zwingenberger K: Extravasation of leukocytes assessed by intravital microscopy: effect of thalidomide. In preparation.
58. Makonkawkeyoon S, Limson-Pobre RNR, Moreira AL, Schauf V, Kaplan G: Thalidomide inhibits the replication of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 90:5974-5978, 1993.
59. Peterson PK, Gekker G, Bornemann M, Chatterjee D, Chao CC: Thalidomide inhibits lipoarabinomannan-induced upregulation of human immunodeficiency virus expression. Antimicrob Agents Chemother 39:28072809, 1995.
60. Gad SM, Shannon EJ, Krotoski WA, Hastings RC: Thalidomide induces imbalances in T-lymphocyte sub-populations in the circulating blood of healthy males. Lepr Rev 56:35-39, 1985.
61. Shannon EJ, Ejigu M, Haile-Mariam HS, Berhan TY, Tasesse G: Thalidomide's effectiveness in erythema nodosum leprosum is associated with a decrease in CD4+ cells in the peripheral blood. Lepr Rev 63:5-11, 1992.
62. Eriksson T, Riesbeck K, Östraat Ö, Ekberg H, Bjorkma S: Drug exposure and flow cytometry analyses in a thalidomide treatment schedule that prolongs rat cardiac graft survival. Transplant Proc 24:2560-2561, 1992.
63. Neubert R, Nogueira AC, Neubert D: Thalidomide derivatives and the immune system. 1. Changes in the pattern of integrin receptors and other surface markers on T lymphocyte subpopulations of marmoset blood. Arch Toxicol 67:1-17, 1993.
64. Nogueira AC, Neubert R, Helge H, Neubert D: Thalidomide and the immune system-3. simultaneous upand down-regulation of different integrin receptors on human white blood cells. Life Sci 55:77-92, 1994.
65. Nogueira AC, Gräfe M, Neubert R: Effect of Thalidomide and some derivatives on the adhesion of lymphocytes to endothelial cells. Naunyn-Schmiedebergs Arch Pharmacol 351 (Suppl):R130, 1995.
66. Arala-Chaves M, Vilanova M, Ribeiro A, Pinto J: I. Immunostimulatory effect of thalidomide in normal C57BL/ 6 Mice is compatible with stimulation of a highly connected central immune system. Scand J Immunol 40:535-542, 1994.
67. Cerruti Mainardi P, Corrone C, Tambussi AM: Richerche sperimentali sull'effetto del-l'imide dell'acido Nftalil-glutammico (talidomide) sulla sintesi degli anticorpi. Resposta aH'iniezione di albumins umana. Med Ped 15:1392-1394, 1963.
68. Dukor P, Dietrich FM: Immunosuppression by thalidomide? Lancet (11 Mar):569-570, 1967.
69. Gusdon JP, Cohen C: Effect of thalidomide on the antibody response. Am J Obstet Gynecol 100:952-956, 1968.
70. Moiraghi Ruggenini A, Errigo E, Bogazzi G: Thalidomide and immunodepression: influence on the antibody's answer to TAB supply and on their natural resistence. G Batteriol Virol Immunol 62:3-15, 1969.
71. Potel J, Brock N: Die immunosuppressive Wirkung verschiedener Cytostatica auf die humorale Antikörperbildung. Arzneim-Forsch/Drug Res 21:1250-1254, 1971.
72. Wemambu SNC, Turk L, Waters MFR, Rees RJW: Erythema nodosum leprosum: A clinical manifestation of the arthus phenomenon. Lancet (1 Nov):933-935, 1969.
73. Miranda RO, Morales MJ, Hastings RC: Thalidomide's effect on antibody formation. Fed Proc, p 1231, 1977.
74. Shannon EJ, Miranda RO, Hastings RC: The effect of thalidomide on de novo antibody synthesis. Int J Lepr 47:381, 1979.
75. Shannon EJ, Miranda RO, Morales MJ, Hastings RC: Inhibition of de novo IgM antibody synthesis by thalidomide as a relevant mechanism of action in leprosy. Scand J Immunol 13:553-562, 1981.
76. Descotes J, Tedone R, Evreux JC: Enhancement of antibody response and delayed-type hypersensitivity by thalidomide in mice. Fundam Clin Pharmacol 2:493497, 1988.
77. Shannon EJ, Truman RW, Christy SA, Brown LM, Vadiee R, Hastings RC: Effect of thalidomide on induction of antibody synthesis in mice to the T-independent antigen, DNP-Ficoll. Lepr Rev 56:297-301, 1985.
78. Koch H: Thalidomide and congeners as anti-inflammatory agents. Prog Med Chem 22:166-242, 1985.
79. Hastings RC, Morales MJ: The effect of thalidomide on neutrophil function. Int J Lepr 46:120, 1978.
80. Jenkins JS, Powell RJ, Allen BR: Investigation of the effect of thalidomide and dapsone on the respiratory burst of normal leucocytes. In Lehner T, Barnes CG (eds): "Recent Advances in Behcet's Disease." London: Royal Society of Medicine Services London, 1986, pp 373-378.
81. Doll NJ, Barnhill RL, Hastings RC, Salvaggio JE, Millikan LE: Thalidomide induced alteration of human peripheral blood monocyte activity. Clin Res 31:920A, 1983.
82. Goihman-Yahr M, Convit J, Rodrîguez-Ochoa G, Aranzazu N, Villalba-Pimentel L, Ocanto A, de Gömez ME: Significance of neutrophil activation in reactional lepromatous leprosy: Effects of thalidomide in vivo and in vitro. Activation in adjuvant disease. Int Arch Allergy Appl Immunol 57:317-332, 1978.
83. Nielsen H, Valerius NH: Thalidomide enhances superoxide anion release from human polymorphonuclear and mononuclear leukocytes. Acta Pathol Microbiol Immunol Scand Sect C Immunol 94:233-237, 1986.
84. Williams KM, Ye W, Lohrer F, Guille J, Day RO, Blaschke G: Effect of thalidomide on polymorphonuclear leukocyte function. Annual Meeting; Australian Rheumatism Association, Perth, December 1991.
85. Miyachi Y, Ozaki M, Uchida K, Niwa Y: Effects of thalidomide on the generation of oxygen intermediates by zymosan-stimulated normal polymorphonuclear leukocytes. Arch Dermatol Res 274:363-367, 1982.
86. Miyachi Y, Ozaki M: Thalidomide does not affect polymorphonuclear leukocyte (PMN) chemotaxis. Nippon Rai Gakkai Zasshi/Jpn J Lepr 50:62-64, 1981.
87. Fauré M, Lejeune JP, Gaucherand M, Thivolet J: PMN leukocytes chemotaxis: Inhibition by thalidomide. Pathol Biol 29:601-604, 1981.
88. Londono F: Thalidomide in the treatment of actinic prurigo. Int J Dermatol 12:326-328, 1973.
89. Charue D, Chauvin E, Duguet C, Revuz J, Bagot M: Thalidomide decreases the production of GM-CSF and TNFcx in mixed epidermal cell lymphocyte reaction. J Invest Dermatol 105:479, 1995.
90. Barkley ASJ, Bather PC, Allen BR: Retinoids enhance monocyte/endothelium interaction. J Invest Dermatol 89:320, 1987.
91. Geitz H, Handt S, Zwingenberger K: Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 31:213-221, 1996.
92. Almenar-Queralt A, Duperray A, Miles LA, Felez J, Altieri DC: Apical topography and modulation of ICAM1 expression on activated endothelium. Am J Pathol 147:1278-1288, 1995.
93. Peterson PK, Hu S, Sheng WS, Kravitz FH, Molrtor TW, Chatterjee D, Chao CC: Thalidomide inhibits tumor necrosis factor-alpha production by lipopolysaccharideand lipoarabinomannan-stimulated human microglial cells. J Infect Dis 172:1137-1140, 1995.
94. Meunier L, Marck Y, Ribeyre C, Meynadier J: Adult cutaneous Langerhans cell histiocytosis: Remission with thalidomide treatment. Br J Dermatol 132:168, 1995.
95. Moncada B, Baranda MC, Gonzâlez-Amaro R, Urbina R, Loredo LE: Thalidomide-effect on T-cell subsets as a possible mechanism of action. Int J Lepr 53:201 -205, 1985.
96. Nogueira AC, Neubert R, Neubert D: Thalidomide-induced alterations in marmoset lymphocytes in culture. Arch Pharm Suppl 2, 344:82, 1991.
97. Neubert R, Nogueira AC, Neubert D: Effect of thalidomide-derivatives on the pattern of lymphocyte subpopulations in marmoset blood. Naunyn-Schmiedebergs Arch Pharmacol 344:R123, 1991.
98. Nogueira AC, Neubert R, Felies A, Jacob-Müller U, Frankus E, Neubert D: Thalidomide derivatives and the immune system. 6. Effects of two derivatives with no obvious teratogenic potency on the pattern of integrins and other surface receptors on blood cells of marmosets. Life Sci 58:337-348, 1996.
99. Thiel R, Förster M, Stahlmann R, Neubert R: Effects of the thalidomide derivative EM12 on surface receptors of peripheral blood lymphocytes in Wistar rats. Teratology 51:30A-31A, 1995.
100. Miranda A, Sampaio EP, Miguel CF, Sarno EN: The influence of thalidomide on the histological manifestations of ENL Int J Lepr 61:99A, 1993.
101. Shannon EJ, Howe RC, McLean K, Hastings RC: Thalidomide does not perturb CD2, CD4, CD5, CD8, HLA-DR or HLA-A, B, C molecules in vitro on the membranes of cells with immune potential. Immunopharmacol Immunotoxicol 16:717-729, 1994.
102. Shannon EJ, McLean K, Howe RC, Hastings RC: Thalidomide does not affect selected immunomodulating surface receptor molecules on cells with immune potential. Int J Lepr 61(4 Suppl):105A, 1993.
103. Jorizzo JL, Schmalstieg FC, Solomon AR, Cavallo T, Taylor RS, Rudioff HB, Schmalstieg EJ, Daniels JC: Thalidomide effects in Behçet's syndrome and pustular vasculitis. Arch Intern Med 146:878-881, 1986.
104. Neubert R, Nogueira AC, Neubert D: Thalidomide and the immune system. 2. Changes in receptors on blood cells of a healthy volunteer. Life Sci 51:2107-2116, 1992.
105. Nogueira AC, Neubert R, Neubert D: Effects of thalidomide on beta 1-integrin receptors in man. NaunynSchmiedebergs Arch Pharmacol 347(Suppl):R110, 1993.
106. Neubert R, Helge H, Neubert D: Thalidomide and the immune system. 4. Down-regulation of the CD26 receptor, probably involved in the binding of HIV components to T cells in primates. Life Sci 56:407-420, 1994.
107. Nishimura K, Hashimoto Y, Iwasaki S: Enhancement of phorbol ester-induced production of tumor necrosis factor alpha by thalidomide. Biochem Biophys Res Commun 199:455-460, 1994.
108. Nishimura K, Hashimoto Y, Iwasaki S: (S)-form of alphamethyl-N(alpha)-phthalimido-glutarimide, but not its (R)-form, enhanced phorbol ester-induced tumor necrosis factor-alpha production by human leukemia cell HL-60: Implication of optical resolution of thalidomidal effects. Chem Pharm Bull 42:1157-1159, 1994.
109. Sasaki K, Shibata Y, Nishimura K, Hashimoto Y, Iwasaki S: Enhancement of 12-0-Tetradecanoylphorbol-13-acetate-induced tumor necrosis factor alpha production by phenethylphthalimide analogs. Biol Pharm Bull 17:1313-1315, 1994.
110. Shibata Y, Shichita M, Sasaki K, Nishimura K, Hashimoto Y, Iwasaki S: N-Alkylphthalimides: Structural requirement of thalidomidal action on 12-0-tetra-decanoylphorbol-13-acetate-induced tumor necrosis factor alpha production by human leukemia HL-60 cells. Chem Pharm Bull 43:177-179, 1995.
111. Sampaio EP, Moreira AL, Sarno EN, Malta AM, Kaplan G: Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients. J Exp Med 175:1729-1737, 1992.
112. Barnes PF, Chatterjee D, Brennan PJ, Rea TH, Modlin RL: Tumor necrosis factor production in patients with leprosy. Infect Immun 60:1441-1446, 1992.
113. Weglicki WB, Stafford RE, Dickens BF, Mak IT, Cassidy MM, Phillips TM: Inhibition of tumor necrosis factoralpha by thalidomide in magnesium deficiency. Mol Cell Biochem 129:195-200, 1993.
114. Ching LM, Xu ZF, Gummer BH, Palmer BD, Joseph WR, Baguley BC: Effect of thalidomide on tumour necrosis factor production and anti-tumour activity induced by 5, 6-dimethylxanthenone-4-acetic acid. Br J Cancer 72:339-343, 1995.
115. Schneider J, Wnendt S, Korioth J, Zwingenberger K: Thalidomide inhibits superantigen-induced TNF-alpha release in mice. 12th European Immunology Meeting of the European Federation of Immunologie Societies, Barcelona/Spain, June 14-17, 1994.
116. Netea MG, Blok WL, Kullberg BJ, Bemelmans M, Vogels MTE, Buurman WA, Meer van der JWM: Pharmacologie inhibitors of tumor necrosis factor production exert differential effects in lethal endotoxemia and in infection with live microorganisms in mice. J Infect Dis 171:393-399, 1995.
117. Helge T, Förster M, Neubert R: Influence of thalidomide and the derivative EM12 on cytokine release by the monocytoid cell line mono MAC 6. Spring Meeting of the German Society of Pharmacology, 1995.
118. Sampaio EP, Kaplan G, Miranda A, Nery JAG, Miguel CP, Viana SM, Sarno EN: The influence of thalidomide on the clinical and immunologie manifestation of erythema nodosum leprosum. J Infect Dis 168:408-414, 1993.
119. Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Ehlers S, Smith KA, Kaplan G: Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 177:1675-1680, 1993.
120. Jasinski M, Wieckiewicz J, Ruggiero I, Pituch NoworoIska A, Zembala M: Isotype-specific regulation of MHC class II gene expression in human monocytes by exogenous and endogenous tumor necrosis factor. J Clin Immunol 15:185-193, 1995.
121. Walchner M, Messer G, Wierenga EA, Przybilla B, Kind P: Reconstitution of transcription factor binding to the conserved lymphokine element-0 and downregulation of NF-kappaB activity after thalidomide treatment of systemic lupus erythematosus. 22nd Annual Meeting of the 'Arbeitsgemeinschaft Dermatologische Forschung', Wuerzburg/Germany, November 1994.
122. Goihman-Yahr M, Requena MA, Vallecalle-Suegart E, Convit J: Autoimmune diseases and thalidomide. I. Experimental allergic encephalomyelitis and experimental allergic neuritis of the guinea pig. Int J Lepr 40:133141, 1972.
123. Goihman-Yahr M, Requena MA, Vallecalle-Suegart E, Convit J: Autoimmune diseases and thalidomide. II. Adjuvant disease, experimental allergic encephalomyelitis and experimental allergic neuritis of the rat. Int J Lepr 42:266-275, 1974.
124. Ulrich M, Salas de B, Convit J: Thalidomide activity in expérimental arthus and anaphylactic reactions. Int J Lepr 39:131-135, 1971.
125. Bosman B: Testing of lipoxygenase inhibitors, cyclooxygenase inhibitors, drugs with immunomodulating properties and some reference antipsoriatic drugs in the modified mouse tail test, an animal model of psoriasis. Skin Pharmacol 7:324-334, 1994.
126. Aarestrup FM, Gonçalves da Costa SC, Sarno EN: The effect of thalidomide on BCG-induced granulomas in mice. Braz J Med Biol Res 28:069-1076, 1995.
127. Arthus M: Repeated injections of equine serum in the rabbit. C R Seances Soc Biol Ses Fil 55:817-820, 1903.
128. Pflum LR, Graeme ML: The arthus reaction in rats, a possible test for anti-inflammatory and antirheumatic drugs. Agents Actions 9:184-189, 1979.
129. Ravetch JV: Fc Receptors: Rubor redux. Cell 78:553560, 1994.
130. Grain E, Mclntosh KR, Gordon G, Pestronk A, Drachman DB: The effect of thalidomide on experimental autoimmune myasthenia gravis. J Autoimmun 2:197-202, 1989.
131. Pfordte K: Über die Beeinflussung des Serumproperidinsystems durch verschiedene Arzneimittel. 1. Mitteilung: Antibiotica, Chemotherapeutica, Antidiabetica,
132. Hypnotica, Immunosuppresiva und Antihyperthyreotica. Pharmazie 26:301-302, 1971.
133. Hastings RC, Morales MJ: Studies of the mechanism of the action of thalidomide in leprosy. Int J Lepr 41:494, 1973.
134. Powell RJ, Alien BR, Jenkins JS, Stele L, Hunneyball I, Maurice PDL, Littlewood SM: Investigation and treatment of orogenital ulcération; studies on a possible mode of action of thalidomide. Br J Dermatol 113:141144, 1985.
135. Gidoh M, Tsutsumi S, Funazu T, Koide S, Marita M: On characteristic antiinflammatory effects of several antileprosy drugs. Nippon Rai Gakkai Zasshi/Jpn J Lepr 48:7-17, 1979.
136. Tsutsumi S, Gidoh M: Inefficacy of thalidomide on rat adjuvant-induced arthritis and lack of arthrogenicity of Hansen bacilli. Nippon Rai Gakkai Zasshi/Jpn J Lepr 57:122-128, 1988.
137. Oliver SJ, Cheng TP, Banguerigo ML, Brahn E: Thalidomide analogues suppress rat collagen arthritis. Arthritis Rheum 38 (6, Suppl):R10, 1995.
138. Burroughs MH, Tsenova-Berkova L, Sokol K, Ossig J, Tuomanen E, Kaplan G: Thalidomide reduces cérébrospinal fluid tumor necrosis factor-alpha release and leukocytosis in experimental meningitis. Microb Pathogen 19:245-255, 1995.
139. Guex-Croisier Y, Pittet N, Herbort CP: The effect of thalidomide and supidimide on endotoxin-induced uveitis in rats. Graefe's Arch Clin Exp Ophthalmol 233:9093, 1995.
140. Vilanova M, Ribeiro A, Carneiro J, Arala-Chaves M: II. The effects of thalidomide treatment on autoimmuneprone NZB and MRC mice are consistent with stimulation of the central immune system. Scand J Immunol 40:543-548, 1994.
141. Lueprasitsakul W, Abend S, Alex S, Reinhardt W, Appel MC, Braverman LE: Effect of thalidomide on the incidence of iodine-induced and spontaneous lymphocytic thyroiditis and spontaneous diabetes mellitus in the BB/Wor rat. Acta Endocrinol 123:79-83, 1990.
142. Stanley HR: Aphthous lesions. Oral Surg Oral Med Oral Pathol 33:407-416, 1972.
143. Shwartzman G: Studies on bacillus typhosus toxic substances. I. Phenomenon of local skin reactivity to B. typhosus culture filtrate. J Exp Med 48:247-268, 1928.
144. Wöhrmann T, Geist C, Schneider J, Matthiesen T, Zwingenberger K: Local skin reactivity after induction of Shwartzman reaction in rabbits. Exp Toxicol Pathol 47:167-172, 1995.
145. Geist C, Woehrmann T, Schneider J, Zwingenberger K: Effects of thalidomide on the local Shwartzman reaction in mice and rabbits. FEMS Immunol Med Microbiol 12:165-174, 1995.
146. Pearson RD, Cox G, Evans T, Smith DL, Weidel D, Castracane J: Wasting and macrophage production of tumor necrosis factor/cachectin and interleukin 1 in experimental visceral leishmaniasis. Am J Trop Med Hyg 43:640-649, 1991.
147. D'Amato RJ, Loughnan MS, Flynn E, Folkman J: Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 91:4082-4085, 1994.
148. D'Amato RJ: Studies examining the effects of thalidomide on angiogenesis. IBC Conference, December 1995.
149. Bore PJ, Scothorne RJ: Effect of thalidomide on survival of skin homografts in rabbits. Lancet (4 Jun):12401241, 1966.
150. Jaffe WP: Failure of thalidomide to influence homograft immunity in chickens. Vet Rec 78:883-884, 1966.
151. Hellman K: Hemmung der Immunisierungsreaktion durch Thalidomid und die Folgen dieses Vorganges für die Theorie derteratogenen Wirkung dieser Substanz. Wiener Med Wochenschrift 15:415-418, 1967.
152. Mouzas GL: Another chance for thalidomide? Lancet (16 Apr):882, 1966.
153. Ellenrieder M, Frankus E, Kriipe W: Immunosuppression durch cyclische Imide bei der Ratte. Klinische Wochenschrift, 45. Jahrg., Heft 22, Nov. 1967, 11591160.
154. Groenewald JH, Weber HW, DeKlerk JN, Murphy GP: Methods of chemical immunosnnnressive treatment in baboon and rhesus monkey allotransplants. In "Medical Primatology 1970. Proc 2nd Conf Exp Med Surg Primates, New York 1969." Basel: Karger, 1971, pp ISO138.
155. Murphy GP, Mirand EA, Groenewald JH, Schoonees R, Weber HW, Brede HD, DeKlerk JN, Zyl van JJW: Erythropoietin release in renal allografted baboons, with and without immunosuppression. Invest Urol 7:271-282, 1970.
156. Murphy GP, Brede HD, Weber HW, Groenewald JH, Williams PD: Thalidomide immunosuppression in canine renal allotransplantation. J Med Exp Clin 1:66-73, 1970.
157. Uthoff K, Zehr KJ, Gaudin PB, Kumar P, Cho PW, Vogelsang G, Hruban RH, Baumgartner WA, Stuart RS: Thalidomide as replacement for steroids in immunosuppression after lung transplantation. Ann Thorac Surg 59:277-282, 1995.
158. Morino F, Olivero S, Vezzosi E, Bezzi P, Ibba F, Fontana D: Results of lung homotransplantation in dogs treated with immunosuppressive drugs. In "Pharmacological Treatment in Organ and Tissue Transplantation." Amsterdam: Excerpta Medica, 1970, pp 290-297.
159. Emre S, Sumrani N, Hong J: Beneficial effect of thalidomide and ciclosporin combination in heterotopic car-diac transplantation in rats. Eur Surg Res 22:336-339, 1990.
160. Tamura F, Vogelsang GB, Reitz BA, Baumgartner WA, Herskowitz A. Combination of thalidomide and cyclosporine for transplantation. Transplant 49:20-25, 1990.
161. Östraat Ö, Ekberg H, Schatz H, Riesbeck K, Eriksson T: Thalidomide prolongs graft survival in rat cardiac transplants. Transplant Proc 24:2624-2625, 1992.
162. Vogelsang GB, Hess AD, Santos GW: Thalidomide for treatment of graft-versus-host disease. Bone Marrow Transplant 3:393-398, 1988.
163. Vogelsang GB, Hess AD, Friedman KJ, Santos GW: Therapy of chronic graft-v-host disease in a rat model. Blood 74:507-511, 1989.
164. Vogelsang GB, Wells MC, Santos GW, Chen TL, Hess AD: Combination low-dose thalidomide and cyclosporine prophylaxis for acute graft-versus-host disease in a rat mismatched model. Transplant Proc 20(2 Suppl 21:226-228, 1988.
165. Vogelsang GB, Farmer ER, Hess AD, Altamonte V, Beschorner WE, Jabs DA, Corio RL, Levin LS, Colvin OM, Wingard JR, Santos GW: Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med 326:1055-1058, 1992.
166. Parker PM, Chao N, Nademanee A, O'Donnell MR, Schmidt GM, Snyder DS, Stein AS, Smith EP, Molina A, Stepan DE, Kashyap A, Planas I, Spielberger R, Somlo G, Margolin K, Zwingenberger K, Wilsmann K, Negrin RS, Long GD, Niland JC, Blume KG, Forman SJ: Thalidomide as salvage therapy for chronic graftversus-host disease. Blood 86:3604-3609, 1995.
167. Suva SRB, Viana PCF, Lugon NV, Hoette M, Ruzany F, Lugon JR: Thalidomide for the treatment of urémie pruritus: A crossover randomized double-blind trial. Nephron 67:270-273, 1994.
168. Sommer C, Myers RR: Inhibition of TNF by thalidomide abolishes an early phase of thermal hyperalgesia in neuropathic rats. Meeting of the Peripheral Nerve Society, Minnesota/USA, June 12-16, 1994.
169. Beuche W, Friede RL: The role of non-resident cells in Wallerian degeneration. J Neurocytol 13:767-796, 1984.
170. Perry VH, Brown MC: Role of macrophages in peripheral nerve degeneration and repair. BioEssays 14:401406, 1992.
171. Stoll G, Jung S, Jander S, Meide van der P, Härtung HP: Tumor necrosis factor-alpha in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system. J Neuroimmunol 45:175182, 1993.
172. Schröder JM, Sellhaus B, Wöhrmann T, Zwingenberger K: Inhibitory effects of thalidomide on cellular proliferation, endoneurial edema and myelin phagocytosis during early Wallerian degeneration. Acta Neuropathol 89:415-419, 1995.
173. Gowans JL: The fate of parenteral strain small lymphocytes in F, hybrid rats. Ann NY Acad Sci 99:432-455, 1962.
174. Shannon EJ, Sandoval F: Thalidomide can be either agonistic or antagonistic to IPS evoked synthesis of TNFa by mononuclear cells. Immunopharmacol Immunotoxicol 18:59-72, 1996.
175. Nathan C, Sporn M: Cytokines in context. J Cell Biol 113:981-986, 1991.
176. Ackermann BA: "Histological analysis of inflammatory skin disease." Philadelphia: Lea and Febinger, 1978, pp 306.
177. Dustin ML, Springer TA: Role of lymphocyte adhesion receptors in transient interactions and cell locomotion. Annu Rev Immunol 9:27-66, 1991.
178. Argenbright LW, Noonan TC: Leukocyte-endothelial adhesion molecules in vivo: A role in physiological function and pathophysiological vasculitides. In Wegner CD (ed): "Adhesion Molecules." London: Academic Press, 1994, pp 209-221.
179. Ley K, Gaethgens P, Fennie C, Singer M, Lasky L, Rosen S: Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo. Blood 77:2553-2565, 1991.
180. Albeda SM, Smith CW, Ward PA: Adhesion molecules and inflammatory injury. FASEB J 8:504-512, 1994.
181. Kishimoto TK: A dynamic model for neutrophil localization to inflammatory sites. J NIH Res 3:75-77, 1991.
182. Weber C, Negrescu E, Erl W, Pietsch A, Frankenberger M, Ziegler-Heitbrock HW, Siess W, Weber PC: Inhibitors of protein tyrosine kinase suppress TNF-stimulated induction of endothelial cell adhesion molecules. J Immunol 155:445-451, 1995.
183. Argenbright LW, Barton RW: Interactions of leukocyte integrins with intercellular adhesion molecule 1 in the production of inflammatory vascular injury in vivo. The Shwartzman reaction revisited. J Clin Invest 89:259272, 1992.
184. Gröger M, Sarmay G, Fiebiger E, Wolff K, Petzelbauer P: Dermal microvascular endothelial cells express CD32 receptors (FcTfilla) in vivo and in vitro. J Immunol 156:1549-1556, 1996.
185. Zadeh HH, Goldschneider I: Demonstration of largescale migration of cortical thymocytes to peripheral lymphoid tissues in cyclosporin A-treated rats. J Exp Med 178:285-293, 1993.
186. Schmidt J, Fleiner S, Heimann-Weitschat I, Lindstaedt R, Szelenyi I: The effect of different corticosteroids and CsA on IL-4 and IL-5 release from murine TH2-type Tcells. Eur J Pharmacol 260:247-250, 1994.
187. Sackstein R: Effects of methylprednisolone administration on lymphocyte Lecam-1, CD44 and LFA-1 expression. Ann NY Acad Sci 696:417-419, 1993.
188. Cockfield SM, Ramassar V, Halloran PF: Regulation of IFN-y and TNF-a expression in vivo. J Immunol 150:342-352.
189. Schmidt J, Fleissner S, Heimann Weitschat I, Lindstaedt R, Pomberg B, Werner U, Szelenyi I: Effect of corticosteroids, cyclosporin A, and methotrexate on cytokine release from monocytes and T-cell subsets. Immunopharmacology 27:173-179, 1994.
190. Kiely PDW, Gillespie KM, Oliveira DBG: Oxpentifylline inhibits TNFa mRNA transcription and protects against arthritis in mercuric chloride-treated Brown-Norway rats. Eur J Immunol 25:2899-2906, 1995.
191. Heinkelein M, Schneider-Schaulies J, Walker BD, Jassoy C: Inhibition of cytotoxicity and cytokine release of CD8+ HIV-specific cytotoxic T lymphocytes by pentoxifylline. J AIDS Hum Retrovirol 10:417-424, 1996.
192. Rott 0, Cash E, Fleischer B: Phosphodiesterase inhibitor pentoxifylline, a selective suppressor of T helper type 1- but not type 2-associated lymphokine produktion, prevents induction of experimental autoimmune encephalomyelitis in Lewis rats. Eur J Immunol 23:1745-1751, 1993.
193. Rosenthal LA, Taub DD, Moors MA, Blank KJ: Methylxanthine-induced inhibition of the antigen- and superantigen-specific activation of T and B lymphocytes. Immunopharmacology 24:203-217, 1992.
194. Teutsch M, Higer M, Wang D, Wortis HW: Induction of CD5 on B and T cells is suppressed by cyclosporin A, FK-520 and rapamycin. Int Immunol 7:381-392, 1995.
195. Svensson U, Holst E, Sundler R: Cyclosporin-sensitive expression of cytokine mRNA in mouse macrophages responding to bacteria. Mol Immunol 32:157-165, 1995.
196. Kim HS, Raskova J, Degiannis D, Raska K: Effects of cyclosporine and rapamycin on immunoglobulin production by preactivated human B cells. Clin Exp Immunol 96:508-512, 1994.
197. Wenzel-Sci fert U, Grünbaum L, Sci fert R: Differential inhibition of human neutrophil activation by cyclosporin A, D and H. J Immunol 147:1940-1946, 1991.
198. Nguyen DT, Eskandari MK, DeForge L, Raiford CL, Strieter RM, Kunkel SL, Remick DG: Cyclosporin A modulation of tumor necrosis factor gene expression. Effect in vitro and in vivo. J Immunol 144:3822-3828, 1990.
199. Weill D, Setiadi H, Wautier MP, Guillausseau PJ, Liote F, Wautier JL: Pharmacological modulation of monocyte adhesion to endothelial cells. Clin Hemorheol 12:713-724, 1992.
200. Geratz JD, Pryzwansky KB, Schwab JH, Anderle SK, Tidwell RR: Suppression of local and systemic responses in streptrococcal cell wall-induced acute in-flammation of the air pouch by cyclosporine A. Am J Pathol 142:1227-1237, 1993.
201. Rao KMK, Crawford J, Currie M, Cohen H: Actin depolymerization and inhibition of capping induced by pentoxifylline in human lymphocytes and neutrophils. J Cell Physiol 137:577-582, 1988.
202. Dogan A, MacDonald TT, Spencer J: Cyclosporin A enhances T cell-mediated induction of E-selectin. Eur J Immunol 23:2922-2926, 1993.
203. Cockerill GW, Bert AG, Ryan GR, Gamble JR, Vadas MA, Cockerill PN: Regulation of granulocyte-macrophage colony-stimulating factor and E-selectin expression in endothelial cells by cyclosporin A and the T-cell transcription factor NFAT. Blood 86:2689-2698, 1995.
204. Caterina de R, Tanaka H, Nakagawa T, Hauptman PJ, Libby P: The direct effect of injectable cyclosporine and its vehicle, cremophor, on endothelial vascular cell adhesion molecule-1 expression. Transplantation 60:270-275, 1995.
205. Pierce JW, Read MA, Ding H, Luscinkas FW, Collins T. Salicylates inhibit licB-phosphorylation, endothelial leukocyte adhesion molecule expression, and neutrophil transmigration. J Immunol 156:3961-3969, 1996.
206. Kovach NL, ündgren CG, Fefer A, Thompson JA, Yednock T, Harlan JM: Pentoxifylline inhibits integrin-mediated adherence of interleukin-2-activated human peripheral blood lymphocytes to human umbilical vein endothelial cells, matrix components, and cultured tumor cells. Blood 84:2234-2242, 1994.
207. Schleimer RP: An overview of glucocorticoid anti-inflammatory actions. Eur J Clin Pharmacol 45 Suppl 1:S3-7, 1993.
208. Gallo RL, Grabbe S, Choi SS, Bleicher P, Granstein R: Cyclosporin increases GM-CSF activity and gene expression in murine keratinocytes. J Invest Dermatol 98:274-278, 1992.
209. Miller RA, Dhen JY, Rea TH, Harnisch JP: Treatment of chronic erythema nodosum leprosum with cyclosporine A produces clinical and immunological remission. Int J Lepr 55:441-449, 1987.
210. Kar HK, Roy RG: Comparison of colchicine and aspirin in the treatment of type 2 lepra reaction. Lepr Rev 59:201-203, 1988.
211. Talhari S, Orsi AT, Talhari AC, Souza FHC, Lima Ferreira de LC: Pentoxifylline may be useful in the treatment of type 2 leprosy reaction. Lepr Rev 66:261-263, 1995.
212. Pacor ML, Biasi D, Lunardi C, Cortina P, Caramaschi P, Girelli D, Botto M, Urbani G, Lombardo G, Lambara LM: Cyclosporin in Behçet's disease: results in 16 patients after 24 months of therapy. Clin Rheumatol 13:224-227, 1994.
213. Simsek H, Dundar S, Telatar H: Treatment of Behçet's disease with indomethacin. Pharmacol Therapeut 30:54-57, 1991.
214. Rofe AM, Whitehouse MW, Bourgeois CS, Haynes DR, Vernon Roberts B: Prevention of adjuvant-induced cachexia in rats by cyclosporin A. Immunol Cell Biol 68:63-69, 1990.
215. Landman D, Sarai A, Sathe SS: Use of pentoxifylline for patients with AIDS-related wasting. Clin Infect Dis 18:97-99, 1994.
216. Klausner JD, Makonkawkeyoon S, Akarasewi P, Nakata K, Kasinerk W, Corral L, Dewar RL, Lane HC, Kaplan G: The effect of thalidomide on the pathogenesis of HIV-1 and M. tuberculosis infection. J Acquir Immune Syndr Hum Retrovirol 11:247-257, 1996.