Refractory ulcers: The role of tumor necrosis factor-α

Journal of the American Academy of Dermatology

Volumn 63, Issue 1, 2010, Pages 146-154

  Weinstein, David A ^a   Kirsner, Robert S ^b  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADALIMUMAB; CERTOLIZUMAB PEGOL; COLLAGEN; CONNECTIVE TISSUE GROWTH FACTOR; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; ETANERCEPT; INFLIXIMAB; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 2; MONOCYTE CHEMOTACTIC PROTEIN 1; PENTOXIFYLLINE; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; VASCULAR CELL ADHESION MOLECULE 1;

ADD ON THERAPY; ANKYLOSING SPONDYLITIS; CHRONIC WOUND; COLLAGEN SYNTHESIS; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; EDITORIAL; HUMAN; KNOCKOUT MOUSE; LEG ULCER; NEUTROPHIL; NONHUMAN; PERIPHERAL VASCULAR DISEASE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION; PSORIATIC ARTHRITIS; RHEUMATOID ARTHRITIS; SKIN INFLAMMATION; SKIN ULCER; STOMACH ULCER; VENOUS PRESSURE; WOUND HEALING;

CHRONIC DISEASE; DERMATITIS; HUMANS; INFLAMMATION; LEG ULCER; SKIN ULCER; TUMOR NECROSIS FACTOR-ALPHA; WOUND HEALING;

EID: 77953260761     PISSN: 01909622     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jaad.2009.08.004     Document Type: Editorial

References (123)

1. Chin G., Diegelmann R., and Schultz G. Cellular and molecular regulation of wound healing. In: Falabella A., and Kirsner R.S. (Eds). Wound healing (2005), Taylor & Francis, Boca Raton 17-37
2. Yager D.R., Chen S., Ward S., Oluyinka O., Diegelmann R.F., and Cohen I.K. Ability of chronic wound fluids to degrade peptide growth factors is associated with increased levels of elastase activity and diminished levels of proteinase inhibitors. Wound Rep Regen 5 (1997) 23-32
3. Brem H., Kirsner R.S., and Falanga V. Protocol for the successful treatment of venous ulcers. Am J Surg 188 (2004) 1-8
4. Lyder C.H. Pressure ulcer prevention and management. JAMA 289 (2003) 223-226
5. Whitney J., Phillips L., Aslam R., Barbul A., Gottrup F., Gould L., et al. Guidelines for the treatment of pressure ulcers. Wound Repair Regen 14 (2006) 663-679
6. Centers for Disease Control and Prevention (CDC). History of foot ulcer among persons with diabetes - United States, 2000-2002. MMWR Morb Mortal Wkly Rep 52 (2003) 1098-1102. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5245a3.htm 2003
7. Centers for Disease Control and Prevention (CDC). National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2007 (2008), Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta: U.S
8. Gordois A., Scuffham P., Shearer A., Oglesby A., and Tobian J.A. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care 26 (2003) 1790-1795
9. Olin J.W., Beusterien K.M., Childs M.B., Seavey C., McHugh L., and Griffiths R.I. Medical costs of treating venous stasis ulcers: evidence from a retrospective cohort study. Vasc Med 4 (1999) 1-7
10. Redelings M.D., Lee N.E., and Sorvillo F. Pressure ulcers: more lethal than we thought?. Adv Skin Wound Care 18 (2005) 367-372
11. Sohn M.W., Lee T.A., Stuck R.M., Frykberg R.G., and Budiman-Mak E. Mortality Risk of Charcot Arthropathy Compared to Diabetic Foot Ulcer and Diabetes Alone. Diabetes Care 32 (2009) 816-821 Epub Feb 5
12. Long-term mortality and its predictors in patients with critical leg ischaemia. The I.C.A.I. Group (Gruppo di Studio dell'Ischemia Cronica Critica degli Arti Inferiori). The Study Group of Criticial Chronic Ischemia of the Lower Exremities. Eur J Vasc Endovasc Surg 14 (1997) 91-95
13. Wang H., Czura C., and Tracey K. Tumor necrosis factor. In: Thomson A., and Lotze M. (Eds). The cytokine handbook (2003), Academic Press, San Diego 837-860
14. Decker T., Lohmann-Matthes M.L., and Gifford G.E. Cell-associated tumor necrosis factor (TNF) as a killing mechanism of activated cytotoxic macrophages. J Immunol 138 (1987) 957-962
15. Engelmann H., Holtmann H., Brakebusch C., Avni Y.S., Sarov I., Nophar Y., et al. Antibodies to a soluble form of a tumor necrosis factor (TNF) receptor have TNF-like activity. J Biol Chem 265 (1990) 14497-14504
16. Engelmann H., Novick D., and Wallach D. Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. J Biol Chem 265 (1990) 1531-1536
17. Hohmann H.P., Remy R., Brockhaus M., and van Loon A.P. Two different cell types have different major receptors for human tumor necrosis factor (TNF alpha). J Biol Chem 264 (1989) 14927-14934
18. Brockhaus M., Schoenfeld H.J., Schlaeger E.J., Hunziker W., Lesslauer W., and Loetscher H. Identification of two types of tumor necrosis factor receptors on human cell lines by monoclonal antibodies. Proc Natl Acad Sci U S A 87 (1990) 3127-3131
19. Tartaglia L.A., Weber R.F., Figari I.S., Reynolds C., Palladino Jr. M.A., and Goeddel D.V. The two different receptors for tumor necrosis factor mediate distinct cellular responses. Proc Natl Acad Sci U S A 88 (1991) 9292-9296
20. Pober J.S., Bevilacqua M.P., Mendrick D.L., Lapierre L.A., Fiers W., and Gimbrone Jr. M.A. Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol 136 (1986) 1680-1687
21. Pohlman T.H., Stanness K.A., Beatty P.G., Ochs H.D., and Harlan J.M. An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-alpha increases neutrophil adherence by a CDw18-dependent mechanism. J Immunol 136 (1986) 4548-4553
22. Gamble J.R., Harlan J.M., Klebanoff S.J., and Vadas M.A. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci U S A 82 (1985) 8667-8671
23. Yang L., Froio R.M., Sciuto T.E., Dvorak A.M., Alon R., and Luscinskas F.W. ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flow. Blood 106 (2005) 584-592
24. Rajan S., Ye J., Bai S., Huang F., and Guo Y.L. NF-kappaB, but not p38 MAP kinase, is required for TNF-alpha-induced expression of cell adhesion molecules in endothelial cells. J Cell Biochem 105 (2008) 477-486
25. Detmar M., and Orfanos C.E. Tumor necrosis factor-alpha inhibits cell proliferation and induces class II antigens and cell adhesion molecules in cultured normal human keratinocytes in vitro. Arch Dermatol Res 282 (1990) 238-245
26. Frater-Schroder M., Risau W., Hallmann R., Gautschi P., and Bohlen P. Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc Natl Acad Sci U S A 84 (1987) 5277-5281
27. Polunovsky V.A., Wendt C.H., Ingbar D.H., Peterson M.S., and Bitterman P.B. Induction of endothelial cell apoptosis by TNF alpha: modulation by inhibitors of protein synthesis. Exp Cell Res 214 (1994) 584-594
28. Vilcek J., Palombella V.J., Henriksen-DeStefano D., Swenson C., Feinman R., Hirai M., et al. Fibroblast growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors. J Exp Med 163 (1986) 632-643
29. Schutze S., Scheurich P., Schluter C., Ucer U., Pfizenmaier K., and Kronke M. Tumor necrosis factor-induced changes of gene expression in U937 cells. Differentiation-dependent plasticity of the responsive state. J Immunol 140 (1988) 3000-3005
30. Solis-Herruzo J.A., Brenner D.A., and Chojkier M. Tumor necrosis factor alpha inhibits collagen gene transcription and collagen synthesis in cultured human fibroblasts. J Biol Chem 263 (1988) 5841-5845
31. Mooney D.P., O'Reilly M., and Gamelli R.L. Tumor necrosis factor and wound healing. Ann Surg 211 (1990) 124-129
32. Regan M.C., Kirk S.J., Hurson M., Sodeyama M., Wasserkrug H.L., and Barbul A. Tumor necrosis factor-alpha inhibits in vivo collagen synthesis. Surgery 113 (1993) 173-177
33. Salomon G.D., Kasid A., Cromack D.T., Director E., Talbot T.L., Sank A., et al. The local effects of cachectin/tumor necrosis factor on wound healing. Ann Surg 214 (1991) 175-180
34. Le J.M., Weinstein D., Gubler U., and Vilcek J. Induction of membrane-associated interleukin 1 by tumor necrosis factor in human fibroblasts. J Immunol 138 (1987) 2137-2142
35. Ito A., Sato T., Iga T., and Mori Y. Tumor necrosis factor bifunctionally regulates matrix metalloproteinases and tissue inhibitor of metalloproteinases (TIMP) production by human fibroblasts. FEBS Lett 269 (1990) 93-95
36. Murphy G., Willenbrock F., Crabbe T., O'Shea M., Ward R., Atkinson S., et al. Regulation of matrix metalloproteinase activity. Ann N Y Acad Sci 732 (1994) 31-41
37. Trengove N., Bielefeldt-Ohmann H., and Stacey M. Mitogenic activity and cytokine levels in non-healing and healing leg ulcers. Wound Rep Regen 8 (2000) 13-25
38. Rao C.N., Ladin D.A., Liu Y.Y., Chilukuri K., Hou Z.Z., and Woodley D.T. Alpha 1-antitrypsin is degraded and non-functional in chronic wounds but intact and functional in acute wounds: the inhibitor protects fibronectin from degradation by chronic wound fluid enzymes. J Invest Dermatol 105 (1995) 572-578
39. Trengove N., Stacey M.C., Macauley S., Bennett N., Gibson J., Burslem F., et al. Analysis of acute and chronic wound environments: the role of proteases and their inhibitors. Wound Rep Regen 7 (1999) 442-452
40. Baker E.A., and Leaper D.J. Proteinases, their inhibitors, and cytokine profiles in acute wound fluid. Wound Repair Regen 8 (2000) 392-398
41. Sakamoto K., Arakawa H., Mita S., Ishiko T., Ikei S., Egami H., et al. Elevation of circulating interleukin 6 after surgery: factors influencing the serum level. Cytokine 6 (1994) 181-186
42. Wallace H.J., and Stacey M.C. Levels of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in chronic venous leg ulcers-correlations to healing status. J Invest Dermatol 110 (1998) 292-296
43. Trengove N., Langton S., and Stacey M. Biochemical analysis of wound fluid from nonhealing and healing chronic leg ulcers. Wound Rep Regen 4 (1996) 234-239
44. Tarnuzzer R.W., and Schultz G.S. Biochemical analysis of acute and chronic wound environments. Wound Repair Regen 4 (1996) 321-325
45. Yager D.R., Zhang L.Y., Liang H.X., Diegelmann R.F., and Cohen I.K. Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids. J Invest Dermatol 107 (1996) 743-748
46. Wysocki A.B., Staiano-Coico L., and Grinnell F. Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol 101 (1993) 64-68
47. Vaalamo M., Weckroth M., Puolakkainen P., Kere J., Saarinen P., Lauharanta J., et al. Patterns of matrix metalloproteinase and TIMP-1 expression in chronic and normally healing human cutaneous wounds. Br J Dermatol 135 (1996) 52-59
48. Bullen E.C., Longaker M.T., Updike D.L., Benton R., Ladin D., Hou Z., et al. Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds. J Invest Dermatol 104 (1995) 236-240
49. Lobmann R., Ambrosch A., Schultz G., Waldmann K., Schiweck S., and Lehnert H. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia 45 (2002) 1011-1016
50. Nwomeh B.C., Liang H.X., Cohen I.K., and Yager D.R. MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers. J Surg Res 81 (1999) 189-195
51. Barnett C.C., Moore E.E., Moore F.A., Biffl W.L., Smith Jr. M.F., and Carl V.S. Intercellular adhesion molecule-1 promotes neutrophil-mediated cytotoxicity. Surgery 118 (1995) 171-175 discussion 176
52. Mori R., Kondo T., Ohshima T., Ishida Y., and Mukaida N. Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration. FASEB J 16 (2002) 963-974
53. Weiss S.J. Tissue destruction by neutrophils. N Engl J Med 320 (1989) 365-376
54. Burnett D., Chamba A., Hill S.L., and Stockley R.A. Effects of plasma, tumour necrosis factor, endotoxin and dexamethasone on extracellular proteolysis by neutrophils from healthy subjects and patients with emphysema. Clin Sci (Lond) 77 (1989) 35-41
55. Richter J., Ng-Sikorski J., Olsson I., and Andersson T. Tumor necrosis factor-induced degranulation in adherent human neutrophils is dependent on CD11b/CD18-integrin-triggered oscillations of cytosolic free Ca2+. Proc Natl Acad Sci U S A 87 (1990) 9472-9476
56. Ladwig G.P., Robson M.C., Liu R., Kuhn M.A., Muir D.F., and Schultz G.S. Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers. Wound Repair Regen 10 (2002) 26-37
57. Dabiri G., and DiPersio C. Matrix metalloproteinases (MMPs). In: Falabella A., and Kirsner R.S. (Eds). Wound healing (2005), Taylor & Francis Group, Boca Raton 49-58
58. Quaglino Jr. D., Nanney L.B., Ditesheim J.A., and Davidson J.M. Transforming growth factor-beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin: incisional wound model. J Invest Dermatol 97 (1991) 34-42
59. Mustoe T.A., Pierce G.F., Thomason A., Gramates P., Sporn M.B., and Deuel T.F. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science 237 (1987) 1333-1336
60. Jude E.B., Blakytny R., Bulmer J., Boulton A.J., and Ferguson M.W. Transforming growth factor-beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers. Diabet Med 19 (2002) 440-447
61. Blakytny R., Jude E.B., Martin Gibson J., Boulton A.J., and Ferguson M.W. Lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers. J Pathol 190 (2000) 589-594
62. Mueller R.V., Hunt T.K., Tokunaga A., and Spencer E.M. The effect of insulinlike growth factor I on wound healing variables and macrophages in rats. Arch Surg 129 (1994) 262-265
63. Mast B.A., and Schultz G.S. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair Regen 4 (1996) 411-420
64. Cowin A.J., Hatzirodos N., Holding C.A., Dunaiski V., Harries R.H., Rayner T.E., et al. Effect of healing on the expression of transforming growth factor beta(s) and their receptors in chronic venous leg ulcers. J Invest Dermatol 117 (2001) 1282-1289
65. Hasan A., Murata H., Falabella A., Ochoa S., Zhou L., Badiavas E., et al. Dermal fibroblasts from venous ulcers are unresponsive to the action of transforming growth factor-beta 1. J Dermatol Sci 16 (1997) 59-66
66. Valencia I.C., Falabella A., Kirsner R.S., and Eaglstein W.H. Chronic venous insufficiency and venous leg ulceration. J Am Acad Dermatol 44 (2001) 22-24 401-21; quiz 22-4
67. Browse N.L., and Burnand K.G. The cause of venous ulceration. Lancet 2 (1982) 243-245
68. Falanga V., and Eaglstein W.H. The "trap" hypothesis of venous ulceration. Lancet 341 (1993) 1006-1008
69. Coleridge Smith P.D., Thomas P., Scurr J.H., and Dormandy J.A. Causes of venous ulceration: a new hypothesis. Causes of venous ulceration: a new hypothesis. Br Med J (Clin Res 296 (1988) 1726-1727
70. Nicolaides AN. Investigation of chronic venous insufficiency: A consensus statement (France, March 5-9, 1997). Circulation 102 (2000) E126-E163
71. Margolis D.J., Berlin J.A., and Strom B.L. Which venous leg ulcers will heal with limb compression bandages?. Am J Med 109 (2000) 15-19
72. Wallace H.J., Vandongen Y.K., and Stacey M.C. Tumor necrosis factor-alpha gene polymorphism associated with increased susceptibility to venous leg ulceration. J Invest Dermatol 126 (2006) 921-925
73. Hajeer A.H., and Hutchinson I.V. Influence of TNFalpha gene polymorphisms on TNFalpha production and disease. Hum Immunol 62 (2001) 1191-1199
74. Murphy M.A., Joyce W.P., Condron C., and Bouchier-Hayes D. A reduction in serum cytokine levels parallels healing of venous ulcers in patients undergoing compression therapy. Eur J Vasc Endovasc Surg 23 (2002) 349-352
75. Ono I., Gunji H., Suda K., Iwatsuki K., and Kaneko F. Evaluation of cytokines in donor site wound fluids. Scand J Plast Reconstr Surg Hand Surg 28 (1994) 269-273
76. Gamm H., Lindemann A., Mertelsmann R., and Herrmann F. Phase I trial of recombinant human tumour necrosis factor alpha in patients with advanced malignancy. Eur J Cancer 27 (1991) 856-863
77. Beck L.S., DeGuzman L., Lee W.P., Xu Y., Siegel M.W., and Amento E.P. One systemic administration of transforming growth factor-beta 1 reverses age- or glucocorticoid-impaired wound healing. J Clin Invest 92 (1993) 2841-2849
78. Charles C.A., Romanelli P., Martinez Z.B., Ma F., Roberts B., and Kirsner R.S. Tumor necrosis factor-alfa in nonhealing venous leg ulcers. J Am Acad Dermatol 60 (2009) 951-955 Epub Apr 2
79. Samlaska C.P., and Winfield E.A. Pentoxifylline. J Am Acad Dermatol 30 (1994) 603-621
80. Neuner P., Klosner G., Schauer E., Pourmojib M., Macheiner W., Grunwald C., et al. Pentoxifylline in vivo down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha by human peripheral blood mononuclear cells. Immunology 83 (1994) 262-267
81. Refsum S.E., Halliday M.I., Campbell G., McCaigue M., Rowlands B.J., and Boston V.E. Modulation of TNF alpha and IL-6 in a peritonitis model using pentoxifylline. J Pediatr Surg 31 (1996) 928-930
82. Strieter R.M., Remick D.G., Ward P.A., Spengler R.N., Lynch III J.P., Larrick J., et al. Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem Biophys Res Commun 155 (1988) 1230-1236
83. Sullivan G.W., Carper H.T., Novick Jr. W.J., and Mandell G.L. Inhibition of the inflammatory action of interleukin-1 and tumor necrosis factor (alpha) on neutrophil function by pentoxifylline. Infect Immun 56 (1988) 1722-1729
84. Santucci L., Fiorucci S., Di Matteo F.M., and Morelli A. Role of tumor necrosis factor alpha release and leukocyte margination in indomethacin-induced gastric injury in rats. Gastroenterology 108 (1995) 393-401
85. Shimizu N., Watanabe T., Arakawa T., Fujiwara Y., Higuchi K., and Kuroki T. Pentoxifylline accelerates gastric ulcer healing in rats: roles of tumor necrosis factor alpha and neutrophils during the early phase of ulcer healing. Digestion 61 (2000) 157-164
86. Delanian S., Balla-Mekias S., and Lefaix J.L. Striking regression of chronic radiotherapy damage in a clinical trial of combined pentoxifylline and tocopherol. J Clin Oncol 17 (1999) 3283-3290
87. Adler P.F. Assessing the effects of pentoxifylline (Trental) on diabetic neurotrophic foot ulcers. J Foot Surg 30 (1991) 300-303
88. Jull A., Arroll B., Parag V., and Waters J. Pentoxifylline for treating venous leg ulcers. Cochrane Database Syst Rev (2007) CD001733
89. Nelson E.A., Prescott R.J., Harper D.R., Gibson B., Brown D., and Ruckley C.V. A factorial, randomized trial of pentoxifylline or placebo, four-layer or single-layer compression, and knitted viscose or hydrocolloid dressings for venous ulcers. J Vasc Surg 45 (2007) 134-141
90. Mirshahi S., Soria J., Mirshahi M., Soria C., Lenoble M., Vasmant D., et al. Expression of elastase and fibrin in venous leg ulcer biopsies: a pilot study of pentoxifylline versus placebo. J Cardiovasc Pharmacol 25 Suppl. 2 (1995) S101-S105
91. Chaudhari U., Romano P., Mulcahy L.D., Dooley L.T., Baker D.G., and Gottlieb A.B. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. Lancet 357 (2001) 1842-1847
92. Ogilvie A.L., Antoni C., Dechant C., Manger B., Kalden J.R., Schuler G., et al. Treatment of psoriatic arthritis with antitumour necrosis factor-alpha antibody clears skin lesions of psoriasis resistant to treatment with methotrexate. Br J Dermatol 144 (2001) 587-589
93. Voigtlander C., Luftl M., Schuler G., and Hertl M. Infliximab (anti-tumor necrosis factor alpha antibody): a novel, highly effective treatment of recalcitrant subcorneal pustular dermatosis (Sneddon-Wilkinson disease). Arch Dermatol 137 (2001) 1571-1574
94. Sullivan T.P., Welsh E., Kerdel F.A., Burdick A.E., and Kirsner R.S. Infliximab for hidradenitis suppurativa. Br J Dermatol 149 (2003) 1046-1049
95. Kobbe G., Schneider P., Rohr U., Fenk R., Neumann F., Aivado M., et al. Treatment of severe steroid refractory acute graft-versus-host disease with infliximab, a chimeric human/mouse antiTNFalpha antibody. Bone Marrow Transplant 28 (2001) 47-49
96. Goossens P.H., Verburg R.J., and Breedveld F.C. Remission of Behcet's syndrome with tumour necrosis factor alpha blocking therapy. Ann Rheum Dis 60 (2001) 637
97. Robertson L.P., and Hickling P. Treatment of recalcitrant orogenital ulceration of Behcets syndrome with infliximab. Rheumatology (Oxford) 40 (2001) 473-474
98. Baughman R.P., and Lower E.E. Infliximab for refractory sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 18 (2001) 70-74
99. Geyer A.S., Anhalt G.J., and Nousari H.C. Effectiveness of infliximab in the treatment of refractory perineal cutaneous Crohn disease. Arch Dermatol 136 (2000) 459-460
100. Mahadevan U., and Sandborn W.J. Infliximab for the treatment of orofacial Crohn's disease. Inflamm Bowel Dis 7 (2001) 38-42
101. Drosou A., Kirsner R.S., Welsh E., Sullivan T.P., and Kerdel F.A. Use of infliximab, an anti-tumor necrosis alpha antibody, for inflammatory dermatoses. J Cutan Med Surg 7 (2003) 382-386
102. Tilg H., Moschen A., and Kaser A. Mode of function of biological anti-TNF agents in the treatment of inflammatory bowel diseases. Expert Opin Biol Ther 7 (2007) 1051-1059
103. von den Driesch P. Pyoderma gangrenosum: a report of 44 cases with follow-up. Br J Dermatol 137 (1997) 1000-1005
104. Bennett M.L., Jackson J.M., Jorizzo J.L., Fleischer Jr. A.B., White W.L., and Callen J.P. Pyoderma gangrenosum. A comparison of typical and atypical forms with an emphasis on time to remission. Case review of 86 patients from 2 institutions. Medicine (Baltimore) 79 (2000) 37-46
105. Tan M.H., Gordon M., Lebwohl O., George J., and Lebwohl M.G. Improvement of pyoderma gangrenosum and psoriasis associated with Crohn disease with anti-tumor necrosis factor alpha monoclonal antibody. Arch Dermatol 137 (2001) 930-933
106. Montoto S., Bosch F., Estrach T., Blade J., Nomdedeu B., and Nontserrat E. Pyoderma gangrenosum triggered by alpha2b-interferon in a patient with chronic granulocytic leukemia. Leuk Lymphoma 30 (1998) 199-202
107. Geren S., Kerdel F., Falabella A., and Kirsner R. Infliximab: A Treatment Option for Ulcerative Pyoderma Gangrenosum. Wounds 15 (2003) 49-53
108. Charles C.A., Leon A., Banta M.R., and Kirsner R.S. Etanercept for the treatment of refractory pyoderma gangrenosum: a brief series. Int J Dermatol 46 (2007) 1095-1099
109. Brooklyn T.N., Dunnill M.G., Shetty A., Bowden J.J., Williams J.D., Griffiths C.E., et al. Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 55 (2006) 505-509
110. Goren I., Muller E., Schiefelbein D., Christen U., Pfeilschifter J., Muhl H., et al. Systemic anti-TNFalpha treatment restores diabetes-impaired skin repair in ob/ob mice by inactivation of macrophages. J Invest Dermatol 127 (2007) 2259-2267
111. Lugering A., Schmidt M., Lugering N., Pauels H.G., Domschke W., and Kucharzik T. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway. Gastroenterology 121 (2001) 1145-1157
112. Shen C., Assche G.V., Colpaert S., Maerten P., Geboes K., Rutgeerts P., et al. Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept. Aliment Pharmacol Ther 21 (2005) 251-258
113. Shen C., Van Assche G., Rutgeerts P., and Ceuppens J.L. Caspase activation and apoptosis induction by adalimumab: demonstration in vitro and in vivo in a chimeric mouse model. Inflamm Bowel Dis 12 (2006) 22-28
114. Loots M.A., Lamme E.N., Zeegelaar J., Mekkes J.R., Bos J.D., and Middelkoop E. Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J Invest Dermatol 111 (1998) 850-857
115. Rosner K., Ross C., Karlsmark T., Petersen A.A., Gottrup F., and Vejlsgaard G.L. Immunohistochemical characterization of the cutaneous cellular infiltrate in different areas of chronic leg ulcers. APMIS 103 (1995) 293-299
116. Streit M., Beleznay Z., and Braathen L.R. Topical application of the tumour necrosis factor-alpha antibody infliximab improves healing of chronic wounds. Int Wound J 3 (2006) 171-179
117. Spriggs D.R., Sherman M.L., Imamura K., Mohri M., Rodriguez C., Robbins G., et al. Phospholipase A2 activation and autoinduction of tumor necrosis factor gene expression by tumor necrosis factor. Cancer Res 50 (1990) 7101-7107
118. Hensel G., Mannel D.N., Pfizenmaier K., and Kronke M. Autocrine stimulation of TNF-alpha mRNA expression in HL-60 cells. Lymphokine Res 6 (1987) 119-125
119. Zhang Y., McCluskey K., Fujii K., and Wahl L.M. Differential regulation of monocyte matrix metalloproteinase and TIMP-1 production by TNF-alpha, granulocyte-macrophage CSF, and IL-1 beta through prostaglandin-dependent and -independent mechanisms. J Immunol 161 (1998) 3071-3076
120. Barnett C.C., Moore E.E., Moore F.A., Biffl W.L., Smith Jr. M.F., and Carl V.S. Intercellular adhesion molecule-1 promotes neutrophil-mediated cytotoxicity. Surgery 118 (1995) 171-175 discussion 6
121. Yagisawa M., Yuo A., Kitagawa S., Yazaki Y., Togawa A., and Takaku F. Stimulation and priming of human neutrophils by IL-1 alpha and IL-1 beta: complete inhibition by IL-1 receptor antagonist and no interaction with other cytokines. Exp Hematol 23 (1995) 603-608
122. Cartwright J.E., Whitley G.S., and Johnstone A.P. The expression and release of adhesion molecules by human endothelial cell lines and their consequent binding of lymphocytes. Exp Cell Res 217 (1995) 329-335
123. Cumberbatch M., Bhushan M., Dearman R.J., Kimber I., and Griffiths C.E. IL-1beta-induced Langerhans' cell migration and TNF-alpha production in human skin: regulation by lactoferrin. Clin Exp Immunol 132 (2003) 352-359