Immunomodulatory therapy associated to anti-parasite drugs as a way to prevent severe forms of malaria

Current Clinical Pharmacology

Volumn 2, Issue 1, 2007, Pages 59-73

  Imaculada Muniz Junqueira, Maria ^a  

^a UNIVERSITY OF BRASILIA   (Brazil)

Author keywords

Adherence molecules; Cerebral malaria; Cytokines; Immunomodulation; Immunopathogenesis; Malaria; Nitric oxidee; Pentoxifylline; Plasmodium falciparum; Reactive oxygen species; Sequestration; Thalidomide; TNF; Tumor necrosis factor

Indexed keywords

ACETYLCYSTEINE; AMODIAQUINE; ANTIMALARIAL AGENT; ARTEMETHER; ARTEMISININ; BUTYLATED HYDROXYANISOLE; CHLOROQUINE; CYTOKINE; DEFEROXAMINE; DEXAMETHASONE; GAMMA INTERFERON ANTIBODY; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ILOPROST; IMMUNOMODULATING AGENT; INTERLEUKIN 12; INTERLEUKIN 6 ANTIBODY; MEFLOQUINE; NITRIC OXIDE; PENTOXIFYLLINE; PLACEBO; PRIMAQUINE; PROGUANIL; PYRIMETHAMINE; QUININE; RECOMBINANT INTERLEUKIN 12; RECOMBINANT TUMOR NECROSIS FACTOR; THALIDOMIDE; TRANSFORMING GROWTH FACTOR BETA ANTIBODY; TUMOR NECROSIS FACTOR ANTIBODY; UNINDEXED DRUG;

ABDOMINAL DISCOMFORT; ANEMIA; ANTIINFLAMMATORY ACTIVITY; ANTIMALARIAL ACTIVITY; BRAIN MALARIA; CLINICAL TRIAL; CYTOKINE PRODUCTION; DEATH; DISEASE SEVERITY; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; HUMAN; IMMUNOMODULATION; IMMUNOPATHOGENESIS; LOW DRUG DOSE; MALARIA; MALARIA CONTROL; MORBIDITY; MORTALITY; NAUSEA; NONHUMAN; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW;

EID: 34248169388     PISSN: 15748847     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488407779422285     Document Type: Review

References (183)

1. World Heath Organization Division of Control of Tropical Diseases. Severe P. falciparum malaria. Trans R Soc Trop Med Hyg 2000; 94 Suppl 1: 1-90.
2. Sachs J, Malaney P. The economic and social burden of malaria. Nature 2002; 415: 680-5.
3. Word Health Organization. World Malaria Report 2005
4. Snow RW, Guerra CA, Noor AM, Myint HI, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 2005; 434:214-217.
5. Greenwood B, Marsh K, Snow R. Why do some African children develop severe malaria? Parasitol Today 1991; 7: 277-81.
6. Marsh K. Malaria - a neglected disease? Parasitology 1992; 104: S53-69.
7. Sitprija V. Nephropathy in falciparum malaria. Kidney Int 1988; 34: 867-77.
8. Warrel DA. Pathophysiology of severe falciparum malaria in man. Parasitology 1987; 94: S53-76.
9. Boulos M, Costa JM, Tosta CE. Comprometimento pulmonar na malária. Rev Inst Med Trop São Paulo 1993; 35: 93-102.
10. Barsoum RS. Malarial nephropathies. Nephrol Dial Transplant 1998; 13: 1588-97.
11. Taylor WRJ, White NJ. Malaria and the lung. Clin Chest Med 2002; 23: 457-68.
12. Naqvi R, Ahmad E, Akhtar F, Naqvi A, Rizvi A. Outcome in severe acute renal failure associated with malaria. Nephrol Dial Transplant 2003; 18: 1820-3.
13. Rasti N, Wahlgren M, Chen Q. Molecular aspects of malaria pathogenesis. FEMS Immunol Med Microbiol 2004; 41: 9-26.
14. Schofield L, Grau GE. Immunological processes in malaria pathogenesis. Nat Rev Immunol 2005; 5: 722-35.
15. Miller LH, Baruch DI, Marsh K, Doumbo OK. The pathogenic basis of malaria. Nature 2002, 415; 673-9.
16. Clark IA, Cowden WB. The pathophysiology of falciparum malaria. Pharmacol Ther 2003; 99: 221-260.
17. Hunt NH, Grau GE. Cytokines: accelarators and brakes in the pathogenesis of cerebral malaria. Trends Immunol 2003; 9: 491-9.
18. Schofield L, Hackett F. Signal transduction in host cell by a glycosylphosphatidylinositol toxin of malaria parasite. J Exp Med 1993; 177: 145-53.
19. Grau GE, Piguet PF, Engers HD, Louis P, Vassali P, Lambert PH. L3T4+ T lymphocytes play a major role in the pathogenesis of murine cerebral malaria. J Immunol 1986; 137:2348-54.
20. Scragg IG, Hensmann M, Bate CA, Kwiatkowski D. Early cytokine induction by Plasmodium falciparum is not a classical endotoxinlike process. Eur J Immunol 1999; 29: 2636-44.
21. Lou J, Lucas R, Grau GE. Pathogenesis of cerebral malaria: recent experimental data and possible applications for humans. Clin Microbiol Rev 14: 810-820; 2001.
22. Urquhart AD. Putative pathophysiological interactions of cytokines and phagocytic cells in severe human falciparum malaria. Clin Infect Dis 1994; 19: 117-31.
23. Eling WMC, Kremsner PG. Cytokines in malaria, pathology and protection. Biotherapy 1994; 7: 211-21.
24. Richards AL. Tumour necrosis factor and associated cytokines in the host's response to malaria. Int J Parasitol 1997; 27:1251-63.
25. Hensmann M, Kwiatkowski D. Cellular basis of early cytokine response to Plasmodium falciparum. Infect Immun 2001; 69: 2364-71.
26. Muniz-Junqueira MI, Santos-Neto LL, Tosta CE. Influence of tumor necrosis factor-α on the ability of monocytes and lymphocytes to destroy intraerythrocytic Plasmodium falciparum in vitro. Cell Immunol 2001; 208, 73-79.
27. Ângulo I, Fresno M. Cytokines in the pathogenesis of and protection against malaria. Clin Diag Lab Immunol 2002; 9: 1145-52.
28. Souza JB, Riley EM. Cerebral malaria: the contribution of studies in animal models to our understanding of immunopathogenesis. Microbes Infect 2002; 4: 291-300.
29. Bate CAW, Taverne J, Playfair JHL. Malarial parasites induce tumour necrosis factor production by macrophages. Immunology 1988; 64, 227-31.
30. Turner G. Cerebral malaria. Brain Pathol 7: 569-582; 1997.
31. Pongponratn E, Turner G, Day NPJ, el al. An ultrastructural study of the brain in fatal Plasmodium falciparum malaria. Am J Trop Med Hyg 2003; 69: 345-9.
32. Picot S, Peyron F, Vuillez JP, Polack B, Ambriose-Thomas P. Chloroquine inhibits tumor necrosis factor production by human macrophages in vitro. J Infect Dis 1991; 164: 830.
33. Kwiatkowski D, Bate C. Inhibition of tumor necrosis factor (TNF) production by antimalarial drugs used in cerebral malaria. Trans R Soc Trop Med Hyg 1995; 89: 215-6.
34. Landewe RBM, Miltenburg AMM, Verndonk MJA, et al. Chloroquine inhibits T- cell proliferation by interfering with IL-2 production and responsiveness. Clin Exp Immunol 1995; 102: 144-51.
35. Udomsangpetch R, Pipitaporn B, Krishna S, et al. Antimalarial drugs reduce cytoadherence and resetting of Plasmodium falciparum. J Infect Dis 1996; 173: 691-8.
36. Goldring JPD, Nemaorani S. Antimalarial drugs modulate the expression of monocyte receptors. Int J Immunopharmacol 1999 21: 599-607.
37. Shalmiev G, Krugliak M, Turrini F, Ginsburg H. Antimalarial drugs inhibit the phagocytosis of erythrocytes infected with Plasmodium falciparum. Trans R Soc Trop Med Hyg 1996; 90: 558-62.
38. Wenisch C, Parschalk B, Zedwitz-Liebenstein K, Wernsdorfer W, Graninger W. The effect of artenisinin on granulocyte function assessed by flow cytometry. J Antimicrob Chemother 1997; 39:99-101.
39. Osorio LM, Fonte L, Finlay CM. Inhibition of human monocyte function by prophylactic doses of chloroquine. Am J Trop Med Hyg 1992; 46: 165-8.
40. Prada J, Muller S, Bienzle U, Kremsner PG. Upregulation of reactive oxygen and nitrogen intermediates in Plasmodium berghei infected mice after rescue therapy with chloroquine or artemether. J Antimicrob Chemother 1996; 38: 95-102.
41. Bloom J. New insights into the molecular basis of glucocorticoid action. Immunol Allergy Clin North Am 1999; 19: 653-70.
42. Warrel DA, Looareesuwan S, Warrel MJ, et al. Dexamethasone proves deleterious in cerebral malaria. N Engl J Med 1982; 306: 313-9.
43. Sliwa K, Grundmann HJ, Neifer S, et al. Prevention of murine cerebral malaria by a stable prostacyclin analog. Infect Imm 1991; 59: 3846-8.
44. Wassmer SC, Cianciolo GJ, Combes V, Grau GE. Inhibition of endothelial activation: a new way to treat cerebral malaria? PLOS Med 2005; 2: 885-90.
45. Clark IA. Does endotoxin cause both the disease and parasite death in acute malaria and babesiosis? Lancet 1978; ii; 75-7.
46. Clark IA, Chaudhri G, Cowden WB. Roles of tumour necrosis factor in the illness and pathology of malaria. Trans R Soc Trop Med Hyg 1989; 83; 436-40.
47. Clark IA Yaman FMA, Jacobson IS. The biological basis of malarial disease. Int J Parasitol 1997; 27: 1237-49.
48. Clark IA, Alleva LM, Mills AC, Cowden WB. Pathogenesis of malaria and clinically similar conditions. Clin Microbiol Rev 2004; 17: 509-39.
49. Grau GE, Fajardo LF, Piquet PF, Lambert PH, Vassali P, 1987. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 1987; 237: 1210-2.
50. Grau GE, Taylor TE, Molyneux ME, Wirima JJ, Vassalli P, Hommel M, Lambert PH. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med 1989; 320; 1586-91.
51. Santos-Neto L, Muniz-Junqueira MI, Tosta CE. Severe cases of Plasmodium falciparum malaria show increased level of both E-selectin and tumor necrosis factor-α. Clin Res 1994; 42: 283A.
52. Rudin W, Eugster H-P, Bordmann G, et al. Resistance to cerebral malaria in tumor necrosis factor-α/β-deficient mice is associated with a reduction of intercellular adhesion molecule-1 up-regulation and T helper type 1 response. Am J Pathol 1997; 150: 257-66.
53. Lucas R, Lou J-N, Juillard P, Moore M, Bluethmann H, Grau GE. Respective role of TNF receptors in the development of experimental cerebral malaria. J Neuroimmunol 1997; 72: 143-8.
54. Grell M, Douni E, Wajant H, et al. The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 1995; 83: 793-802.
55. Kwiatkowski D, Molyneux ME, Stephens S, et al. Anti-TNF therapy inhibits fever in cerebral malaria. QJ Med 1993; 86: 91-8.
56. van Hensbrock MB, Palmer A, Onyorah E, et al. The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria. J Infect Dis 1996; 174: 1091-7.
57. Doherty GM, Jensen JC, Alexander HR, Buresh CM, Norton JA. Pentoxifylline suppression of tumor necrosis factor gene transcription. Surgery 1991; 110: 192-8.
58. Zabel P, Schade FU, Schlaak M. Inhibition of endogenous TNF formation by pentoxifylline. Immunobiology 1993; 187: 447-63.
59. Strieter RM, Remick DG, Ward PAI. Cellular and molecular regulation of tumor necrosis factor release from macrophages. Biochem Biophys Res Commun 1988; 155: 1230-6.
60. Ward A, Clissold SP. Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy. Drugs 1987; 34: 50-97.
61. Hand WL, Butera ML, King-Thompson NL, Hand DL. Pentoxifylline modulation of plasma membrane functions in human polymorphonuclear leukocytes. Infect Immun 1989; 57: 3520-6.
62. Crouch SPM, Fletcher J. Effect of ingested pentoxifylline on neutrophil superoxide anion production. Infect Immun 1992; 60: 4504-09.
63. Kozaki K, Egawa H, Bermudes L, Feduska NJ, So S, Esquivel CO. Pentoxifylline inhibits production of superoxide anion and tumor necrosis factor by Kupffer cells in rat liver preservation. Transplant Proc 1993; 25: 3025-26.
64. Kriska M, Kristová V, Turcáni P. Pentoxifylline- a pharmacodynamically versatile agent. Slovakofarma Revue VIII 1998; 2: 41-7.
65. Neuner P, Klosner G, Schauer M, et al. Pentoxifylline in vivo down-regulates the release of IL-1β, IL-6, IL,8 and tumour necrosis factor-α by human peripheral blood mononuclear cells. Immunology 1994; 83: 262-7.
66. Prada J, Prager C, Neifer S, Bienzle U, Kremsner PG. Production of interleukin-6 by human and murine mononuclear leukocytes stimulated with Plasmodium antigens enhanced by pentoxifylline, and tumor necrosis factor secretion is reduced. Infect Immun 1993; 61: 2737-40.
67. Mandell GL. Cytokines, phagocytes, and pentoxifylline. J Cardiovasc Pharmacol 1995; 25 (Suppl): 20-22.
68. Lehman LG, Vu-Quoc B, Carlson J, Kremsner PG. Plasmodium falciparum: inhibition of erythrocyte rosette formation and detachment of rosettes by pentoxifylline. Trans R Soc Trop Med Hyg 1997; 91: 74-5.
69. Kremsner PG, Grundmann H, Neifer S, et al. Pentoxifylline prevents murine cerebral malaria. J Infect Dis 1991; 164: 605-8.
70. Santos-Neto L, Muniz-Junqueira MI, Brandt MC, Tosta CE. Has pentoxifylline a place in the therapy of malaria? Rev Soc Brasil Med Trop 1992; 25 (Suppl II); 66-7.
71. Di Perri G, Di Perri IG, Badona G, et al. Pentoxifylline as a supportive agent in the treatment of cerebral malaria in children. J Infect Dis 1995; 171: 1317-22.
72. Graninger W, Thalhammer F, Locker G. Pentoxifylline in cerebral malaria. J Infect Dis 1991; 164: 829.
73. Hemmer CJ, Hort G, Chiwakata CB, et al. Supportive pentoxifylline in falciparum malaria: no effect on tumor necrosis factor alpha levels or clinical outcome: a prospective, randomized, placebo-controlled study. Am J Trop Med Hyg 1997; 56: 397-403.
74. Looareesuwan S, Wilairatana P, Vanaratana V, et al. Pentoxifylline as an ancillary treatment for severe falciparum malaria in Thailand. Am J Trop Med Hyg 1998; 58: 348-53.
75. Stoltenburg-Didinger G, Neifer S, Bienzle U, Eling WMC, Kremsner PG. Selective damage of hippocampal neurons in murine cerebral malaria prevented by pentoxifylline. J Neurol Sci 1993; 114: 20-4.
76. Wenisch C, Looareesuwan S, Wilairatana P, et al. Effect of pentoxifylline on cytokine patterns in the therapy of complicated Plasmodium falciparum malaria. Am J Trop Med Hyg 1998; 58: 343-7.
77. Calabrese L, Fleischer A.B. Thalidomide: current and potential clinical applications. Am J Med 2000; 108: 487-95.
78. Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G. Thalidomide selectively inhibits tumor necrosis factor-α production by stimulated human monocytes. J Exp Med 1991; 173: 699-703.
79. Sampaio EP, Kaplan G, Miranda A, Nery JAC, Miguel CP, Viana SM, Sarno EM. The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum. J Infect Dis 1993; 168: 408-14.
80. Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G. Thalidomide exerts its inhibitory action on tumor necrosis factor-α by enhancing mRNA degradation. J Exp Med 1993; 177: 1675-80.
81. Corral L, Kaplan G. Immunomodulation by thalidomide and thalidomide analogues. Ann Rheum Dis 1999; 58 (Suppl 1), 1107-13.
82. Moller DR, Wysocka M, Greenlee BM, Ma X, Wahl L, Flockhart DA, Trinchieri G, Karp CL. Inhibition of IL-12 production by thalidomide. J. Immunol 1997; 159: 5157-61.
83. Geitz H, Handt S, Zwingenberger K. Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 1996: 31: 213-21.
84. Zwingenberger K, Wnendt S. Immunomodulation by thalidomide: systematic review of the literature and of unpublished observations. J Inflamm 1996: 46: 177-211.
85. Teo SK, Stirling DI, Zeldis JB. Thalidomide as a novel therapeutic agent: new uses for an old product Drug Discov Today 2005; 10: 107-14.
86. Ramirez-Villafuertes JM, Oltra-Ramirez A, Favila-Castillo L. The effect of thalidomide on parasitemia, antibody response, anemia and blood glucose in CB6F1 mice infected with Plasmodium chabaudi chabaudi AS. Parasitol Int 1998; 47 (Suppl): 346.
87. Muniz-Junqueira MI, Silva FO, Paula-Júnior MR, Tosta CE. Thalidomide influences the function of macrophages and increases the survival of Plasmodium berghei-infected CBA mice. Acts Trop 2005; 94: 128-38.
88. Postma NS Hermsen CC, Crommelin DJ, Zuidema J, Eling WM. Treatment with recombinant human tumour necrosis factor-alpha reduces parasitaemia and prevents Plasmodium berghei K173-induced experimental cerebral malaria in mice. Parasitology 1999 118: 7-15.
89. Postma NS Hermsen CC, Crommelin DJ, Eling WM, Zuidema J. Thiolated recombinant human tumor necrosis factor-alpha protects against Plasmodium berghei K173-induced experimental cerebral malaria in mice. Antimicrob Agents Chemother 1999 43: 1027-33.
90. Postma NS Hermsen CC, Crommelin DJ, Eling WM, Zuidema J. Treatment with liposome-bound recombinant human tumor necrosis factor-α suppresses parasitemia and protects against Plasmodium berghei K173-induced experimental cerebral malaria in mice. J Pharmacol Exp Ther 1999; 288: 114-20.
91. Grau GE, Heremans H, Piguet PF, et al. Monoclonal antibody against inferferon-gamma can prevent experimental cerebral malaria an its associated overproduction of tumor necrois factor. Proc Natl Acad Sci USA 1989; 86: 5572-4.
92. Tsutsui N, Kamiyama T. Transforming growth factor β-induced failure of resistance to infection with blood-stage Plasmodium chabaudi in mice. Infect Immun 1999; 67: 2306-11.
93. Grau GE, Kindler V, Piguet P-F, Lambert P-H, Vassali P. Prevention of experimental cerebral malaria by anticytokine antibodies. J Exp Med 1988; 168: 1499-504.
94. Grau GE, Frei K, Piguet P-F, Fontana A, Heremans H, Billiau A, Vassalli P, Lambert P-H. Interleukin 6 production in experimental cerebral malaria: modulation of antocytokine antibodies and possible role in hypergammaglobulinemia J Exp Med 1990; 172: 1505-8.
95. Stevenson MM, Tam MF, Wolf SF, Sher A. IL-12 induced protection against blood-stage Plasmodium chabaudi AS requires IFN-γ and TNF-α and occurs via a nitric oxide dependent mechanism. J Immunol 1995; 155: 2545-56
96. Sedegah M, Finkelman F, Hoffman SL. Interleukin 12 induction of interferon γ- dependent protection against malaria. Proc Natl Acad Sci USA 1994; 91: 10700-2.
97. Hoffman SL, Crutcher JM, Puri SK et al. Sterile protection of monkeys against malaria after administration of interleukin-12. Nat Med 1997; 3: 80-3.
98. Haque A, Echchannaoui H, Seguin R, Schwartzman J, Kasper LH, Haque S. Cerebral malaria in mice. Interleukin-2 treatment induces accumulation of γδT cells in the brain and alters resistant mice to susceptible-like phenotype. Am J Pathol 2001; 158: 163-72.
99. Kossodo S, Grau GE. Profiles of cytokine production in relation with susceptibility to cerebral malaria. J Immunol 1993; 151: 4811-20.
100. Winkler S, Wilheim M, Baier K et al. Reciprocal regulation of Th1 and Th2 cytokine-producing T cells during clearance of parasitemia in Plasmodium falciparum malaria. Infec Immun 1998; 66: 6040-4.
101. Day NPJ, Hien TT, Schollaardt T, Loc PP, Chuong LV, Chau TTH, Mai TH, Phu NH, Sinh DX, White NJ, Ho M. The prognostic and pathophysiologic role of pro-and antiinflammatory cytokines in severe malaria. J Infect Dis 1999; 180: 1288-97.
102. Riley EM. Is T cell priming required for initiation of pathology in malaria infection? Immunol Today 1999; 20: 228-33.
103. Musumeci M, Malaguarnera L, Simporè J, Messina A, Musumeci S. Modulation of immune response in Plasmodium falciparum malaria: role of IL- 12, IL-18 and TGF-β. Cytokine 2003; 21: 172-8.
104. Wipasa J, Elliott S, Xu H, Good MF. Immunity to asexual blood stage malaria and vaccine approaches. Immunol Cell Biol 2002; 80: 401-14.
105. Malaguarnera L, Musumeci S. The immune response to Plasmodium falciparum malaria. Lancet Infect Dis 2002; 2: 472-8.
106. Othoro C, Lal AA, Nahlen B, Koech D, Orago ASS, Udhayakumar V. A low interleukin-10 tumor necrosis factor-α ratio is associated with malaria anemia in children residing in a holoendemic malaria region in Western Kenya. J Infect Dis 1999; 179: 279-82.
107. Li C, Sanni LA, Omer F, Riley E, Langhorne J. Pathology of Plasmodium chabaudi chabaudi infection and mortality in interleukin-10 deficient mice are ameliorated by anti- tumor necrosis factor alpha and exacerbated by anti- transforming growth factor β antibodies. Infect Immun 2003; 71: 4850-6.
108. Perkins DJ, Weinberg JB, Kremsner PG. Reduced interleukin-12 and transforming growth factor-β1 in severe childhood malaria: relationship of cytokine balance with disease severity. J Infect Dis 2000; 182: 988-92.
109. Malaguarnera L, Imbesi RM, Pignatelli S; Simpore J, Malaguarnera M, Musumeci S. Increased levels of interleukin-12 in Plasmodium falciparum malaria: correlation with severity of disease. Parasite Immunol 2002; 24: 387-9.
110. Malaguarnera L, Pignatelli S, Musumeci M, Simpore J, Musumeci S. Plasma levels of interleukin-18 and interleukin-12 in Plasmodium falciparum malaria. Parasite Immunol 2002; 24: 489-92.
111. Malaguarnera L, Pignatelli S, Simpore J, Malaguarnera M, Musumeci S. Plasma levels of interleukin-12 (IL-12), interteukin-18 (IL-18) and transforming growth factor beta (TGF-beta) in Plasmodium falciparum malaria. Eur Cytokine Netw 2002; 13: 425-30.
112. Chaisavaneeyakorn S, Othoro C, Shi YP, Otieno J, Chaiyaroj SC, La1 AA, Udhayakumar V. Relationship between plasma interleukin-12 (IL-12) and IL-18 levels and severe malarial anemia in an area of holoendemicity in Western Kenya. Clin Diagn Lab Immunol 2003; 10: 362-366.
113. Luty AJF, Perkins DJ, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Weinberg JB, Kremsner PG. Low interleukin-12 activity in severe Plasmodium falciparum malaria. Infect Immun 2000; 68: 3909-15.
114. Omer FM, Souza JB, Riley EM. Differential induction of TGF-β regulates proinflammatory cytokine production and determines the outcome of lethal and nonlethal Plasmodium yoelii infections. J Immunol 2003; 171: 5430-6
115. Omer FM, Riley EM. Transforming growth factor β production is inversely correlated with severity of murine malaria infection. J Exp Med 1998; 188: 39-48.
116. Stevenson MM, Su Z, Sam H, Mohan K. Modulation of host responses to blood-stage malaria by interleukin-12: from therapy to adjuvant activity. Microbes Infect 2001; 3: 49-59.
117. Omer FM, Kurtzhals JA, Riley EM. Maintaining the immunological balance in parasitic infections: a role for TGF-beta? Parasitol Today 2000; 16: 18-23.
118. Kurtzhals JAL, Akanmori BD, Goka BQ, Adabayeri V, Nkrumah FK, Behr C, Hviid L. The cytokine balance in severe malaria anemia. J Infect Dis 1999; 180: 1753-4.
119. MacPherson GG, Warrel MJ, White NJ. Looareesuwan S, Warrel DA. Human cerebral malaria. A quantitative ultra-structural analysis of parasitized erythrocyte sequestration. J Pathol 1985; 119: 385-401.
120. Ho M, White NJ. Molecular mechanisms of cytoadherence in malaria. Am J Physiol 1999; 276; C1231-42.
121. Chen Q, Schlichtherle M, Wahlgren M. Molecular aspects of severe malaria. Clin Microbiol Rev 2000; 13: 439-450.
122. Grau GE, Pointaire P, Piguet PF, Vesin C, Rosen H, Stamenkovic I, Takei F, Vassali P. Late administration of monoclonal antibody to leukocyte function- antigen 1 abrogates incipient murine cerebral malaria. Eur J Immunol 1991; 21: 2265-7.
123. Falanga PB, Butcher EC. Late treatment with anti-LFA-1 (CD11a) antibody prevents cerebral malaria in a mouse model. Eur J Immunol 1991; 21: 2259-63.
124. Combes V, Rosenkranz AR, Redard M, et al. Pathogenic role of P-selectin in experimental cerebral malaria. Importance of the endothelial compartment. Am J Pathol 2004; 164: 781-6.
125. Wassmer SC, Combes V, Grau GE. Pathophysiology of cerebral malaria: role of host cells in the modulation of cytoadhesion. Ann N Y Acad Sci 2003; 992: 30-8.
126. Newton CRJC, Taylor TE, Whitten RO. Pathophysiology of fatal falciparum malaria in African children. Am J Trop Med Hyg 1998; 58: 673-83.
127. Silamut Y, Phu NH, Whitty C, et al. A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain. Am J Pathol 1999; 155: 395-410.
128. Taylor TE, Fu WJ, Carr RA et al. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 2004; 10: 143-5.
129. Turner GDH, Morrison H, Jones M, et al. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol 1994; 145: 1057-69.
130. Sherman IW, Eda S, Winograd E. Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind. Microbes Infect 2003; 5: 897-909.
131. Cooke BM, Mohandas N, Cowman AF, Coppel RL. Cellular adhesive phenomena in apicomplexan parasites or red blood cells. Vet Parasitol 2005; 132: 273-95.
132. Lucas R, Lou J, Morel DR, Ricou B, Suter PM, Grau GE. TNF receptors in the microvascular pathology of acute respiratory distress syndrome and cerebral malaria. J Leukoc Biol 1997; 61: 551-8.
133. Dondorp A, Pongponratn E, White NJ. Reduced microcirculatory flow in severe falciparum malaria: pathophysiology and electron-microscopic pathology. Acta Trop 2004; 89: 309-17.
134. Favre N, Laperousaz C, Ryffel NA, Imhof BA, Rudin W, Lucas R, Piguet PF. Role of ICAM-1 (CD54) in the development of murine cerebral malaria. Microbes Infect 1999; 1: 961-8.
135. Grau GE, Tacchini-Cottier F, Vesin C, Milon G, Lou JN, Piguet PF, Juillard P. TNF-induced microvascular pathology: active role for platelets and importance of the LAF-1/ICAM-1 interaction. Eur Cytokine Netw 1993; 4: 415-9.
136. Grau GE, Mackenzie CD, Carr RA, et al. Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis 2003; 187: 461-6.
137. Wassmer SC, Lépolard C,Traoré B, Pouvelle B, Gysin J, Grau GE. Platelets reorient Plasmodium falciparum-infected erytrhocyte cytoadhesion to activated endothelial cells. J Infect Dis 2004; 189: 180-9.
138. Ehrhardt C, Kneuer C,Bakowsky U. Selectins- an emerging target for drug delivery. Adv Drug Deliv Rev 2004; 56: 527-49.
139. Hviid L, Theander TG, Elhassan IM, Jensen JB. Increased plasma levels of soluble ICAM-1 and ELAM-1 (E-selectin) during acute Plasmodium falciparum malaria. Immunol Letters 1993; 36: 51-8.
140. Jakobsen PH, Morris-Jones S, Ronn A, Hviid L, Theander TG, Elhassan IM, Bygbjerg IC, Greenwood BM. Increased plasma concentration of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity. Immunology 1994; 83: 665-9.
141. Santos-Neto L, Muniz-Junqueira MI, Tosta CE. Severe cases of Plasmodium falciparum malaria show increased plasma level of both E-selectin and tumor necrosis factor-α. Clin Res 1994; 42: 283A.
142. Wenisch C, Varijanonta S, Looareesuwan S, et al. Soluble intercellular adhesion molecule 1-(ELAM-1), and tumor necrosis factor receptor (55kDa TNF-R) in patients with acute Plasmodium falciparum malaria. Clin Immnol Immunopathol 1994; 71: 344-8.
143. Diamond M, Staunton DE, Fougerolles AR, et al. ICAM-1 (CD54): a counter receptor for Mac-1 (CD11b/CD18). J Cell Biol 1990; 111: 3129-39.
144. Craig AG, Pinches R, Khan S, Roberts DJ, et al. Failure to block adhesion of Plasmodium falciparum-infected erythrocytes to ICAM-1 with soluble ICAM-1. Infect Immun 1997; 65: 4580-5.
145. Chakravorty SJ, Craig A. The role of ICAM-1 in Plasmodium falciparum cytoadherence. Eur J Cell Biol 2005; 84:15-27.
146. Clark IA, Awburn MM, Harper CG, Liomba NG, Molyneux ME. Induction of HO-1 in tissue macrophages and monocytes in fatal falciparum malaria and sepsis. Malar J 2003, 2: 41-53.
147. McCormick CJ, Craig A, Roberts D, Newbold CI, Berendt AR. Intercellular adhesion motecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells. J Clin Invest 1997; 100: 2521-9.
148. Luscinskas FW, Ma S, Nusrat A, Parkos CA,Sunil K. Shawa SK. Leukocyte transendothelial migration: A junctional affair. Semin Immunol 2002;14, 105-13.
149. Kikuchi M, Looareesuwan S, Ubalee R, et al. Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais. Parasitol Int 2001; 50: 235-39.
150. Heddini A. Malaria pathogenesis: a jigsaw with an increasing number of pieces. Int J Parasitol 2002; 32: 1587-98.
151. Treutiger CJ, Heddini A, Fernández V, Muller WA, Wahlgren M. PECAM/CD31, an endothelial receptor for binding Plasmodium falciparum- infected erythrocytes. Nat Med 1997; 3: 1405-8.
152. Brown H, Turner G, Rogerson S, et al. Cytokine expression in the brain in human cerebral malaria. J Infect Dis 1999; 180: 1742-6.
153. Ockenhouse CF, Tegoshi T, Maeno Y, et al. Human vascular endotelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endotelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. J Exp Med 1992; 176: 1183-9.
154. Heddini A, Pettersson F, Kai O, et al. Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors. Infect Immun 2001; 69: 5849-56.
155. Weitz-Schmidt G. Statins as anti-inflammatory agents. Trends Pharmacol Sci 2002; 23: 482-6.
156. Sherer Y, Shoenfeld Y. Immunomodulation for treatment and prevention of atherosclerosis. Autoimmun Rev 2002; 1: 21-7.
157. Muniz-Junqueira MI, Karnib SR, Paula-Coelho VN, Junqueira Jr LF. Effects of pravastatin on the in vitro phagocytic function and hydrogen peroxide production by monocytes of healthy individuals. Int Immunopharmacol 2006; 6: 53-60.
158. Lefer DJ. Pharmacology of selectin inhibitors in ischemia/reperfusion states. Ann Rev Pharmacol Toxicol 2000; 40: 283-94.
159. Tucker GC. Inhibitors of integrins. Curr Op Pharmacol 2002; 2: 394-402.
160. Vanderslice P, Biediger RJ, Woodside DG, Berens KL, Holland GW, Dixon RAF. Development of cell adhesion molecule antagonists as therapeutics for asthma and COPD. Pulm Pharmacol Ther 2004; 17: 1-10.
161. González-Amaro R, Mittelbrunn M, Sánchez-Madrid F. Therapeutic anti- integrin (α4 and αL) monoclonal antibodies: two-edged swords? Immunology 2005; 116: 289-96.
162. Simmons DL. Anti-adhesion therapies. Curr Op Pharmacol 2005; 5: 389-404.
163. Dockrell HM, Playfair JH. Killing of blood-stage murine malaria parasites by hydrogen peroxide. Infect. Immun 1983; 39: 456-9.
164. Ockenhouse CF, Shear HL. Oxidative killing of the intraerythrocytic malaria parasite Plasmodium yoelii by activated macrophages. J Immunol 1984 132, 424-431.
165. Thumwood CM, Hunt NH, Cowden WB, Clark IA. Antioxidants can prevent cerebral malaria in Plasmodium berghei-infected mice. Br J Exp Pathol 1989; 70: 293-303.
166. Stevenson MM, Huang DY, Podoba JE, Nowotarski ME. Macrophage activation during Plasmodium chabaudi AS infection in resistant C57BL/6 and susceptible A/J mice. Infect Immun 1992; 60: 1193-201.
167. Gyan B, Troye-Blomberg M, Perlmann P, Björkman A. Human monocytes cultured with and without interferon-gamma inhibit Plasmodium falciparum parasite growth in vitro via secretion of re-active nitrogen intermediates. Parasite Immunol 1994; 16: 371-5.
168. Kremsner PG, Winkler S, Wildling E, Prada J, Bienzle U, Graninger W, Nüssler AK, 1996. High plasma levels of nitrogen oxides are associated with severe disease and correlate with rapid parasitological and clinical cure in Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 1996;90: 44-7.
169. Odeh, M. The role of tumour necrosis factor-α in the pathogenesis of complicated falciparum malaria. Cytokine 2001; 14: 11-8.
170. Becker K, Tilley L, Vennerstrom JL, Roberts D, Rogerson S, Ginsburg H. Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions. Int J Parasitol 2004; 34: 163-89.
171. Rockett KA, Targett GAT, Playfair JHL, 1988. Killing of blood-stage Plasmodium falciparum by tipid peroxides from tumor necrosis serum. Infect. Immun 1988; 56: 3180-3.
172. Das BS, Patnaik JK, Mohanty S. Plasma antioxidants and lipid peroxidation products in falciparum malaria. Am J Trop Med Hyg 1993; 49? 720-25.
173. Malhotra K, Salmon D, Le-Bras J, Vilde JL. Susceptibility of Plasmodium falciparum to peroxidase-mediated oxygen-dependent microbicidal system. Infect. Immun 1988; 56: 3305-09.
174. Descamps-Latscha B, Lunel-Fabiani F, Kara-Binis A, Druilhe P. 1987. Generation of reactive oxygen species in whole blood from patients with acute filciparum malaria. Parasite Immunol 1987; 9: 275-9.
175. Clark, I.A., Chaudhri, G., Cowden, W.B. Some roles of free radicals in malaria. Free Radic Biol Med 1989; 6, 315-321.
176. Thuma PE, Mabeza GF, Biemba G, et al. Effect of iron chelation therapy on mortality in Zambian children with cerebral. Trans R Soc Trop Med Hyg 1998; 92: 214-8.
177. Watt G, Jongsakul K, Ruangvirayuth R. A pilot study of N-acetylcysteine as adjunctive therapy for severe malaria. Q J Med 2002; 95: 285-90.
178. Sobolewski P, Gramaglia I, Frangos J, Intaglietta M, van der Heyde HC. Nitric oxide bioavailability in malaria. Trends Parasitol 2005; 21: 415-22.
179. Rockett KA, Awburn MM, Cowden WB, Clark IA. Killing of Plasmodium falciparum in vitro by nitric oxide derivatives. Infect Immun 1991; 59: 3280-3.
180. Prada J, Kremsner PG. Enhanced production of reactive nitrogen intermediates in human and murine malaria. Parasitol Today 1995; 11: 409-410.
181. Weiss G, Thuma. PE, Biemba G, Mabeza G, Werner ER, Gordeuk VR. 1998. Cerebral fluid levels of biopterin, nitric oxide metabolites, and immune activation markers and the clinical course of human cerebral malaria. J Infect Dis 1998; 177: 1064-8.
182. Maneerat Y, Viriyavejakul P, Punpoowong B, et al. Inducible nitric oxide synthase expression is increased in the brain in fatal cerebral malaria. Histopathology 2000; 37: 269-77.
183. Warrel DA. Management of severe malaria. Parassitologia 1999; 41: 287-94.