Skip to main content
SpringerLink
Log in

Decreased serum levels of TGF-β in patients with acutePlasmodium falciparum malaria

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Apart from cellular immunity and immunopathology, various cytokines have been implicated in malaria-associated immunosuppression. In this study, serum levels of transforming growth factor-β (TGF-β) were determined with an enzyme-linked immunosorbent assay in 37 patients with acutePlasmodium falciparum malaria prior to, during, and after therapy and in 17 healthy controls in Bangkok, Thailand. Patients were treated with artesunate and mefloquine. TGF-β serum levels were found decreased prior to treatment (14±11 pg/ml versus 63±15 pg/ml in healthy controls;P<0.05). The serum concentrations of TGF-β increased after initiation of treatment and were within normal range on day 21. Serum levels of both tumor necrosis factor-ga (TNF-α) and soluble TNF-receptor 55 kDa were inversely correlated to serum levels of TGF-β (r= −0.667 andr=}-0.592, n=37; respectively,P < 0.05 for both). No correlation between parasitemia and serum levels of TGF-β could be found. The results are compatible with a decreased production and release, an enhanced clearance or utilization, or tissue accumulation of TGF-β in acuteP. falciparum malaria.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sher A, Gazzinelli RT, Oswald IP, Clerici M, Kullberg M, Pearce EJ, Berzofsky JA, Mosmann TR, James SL, Morse HC, Shearer GM: Role of T-cell derived cytokines in the downregulation of immune-responses in parasitic and retroviral infection. Immunol Rev 127:183–204, 1992

    PubMed  Google Scholar 

  2. Silva JS, Twardzik DR, Reed SG: Regulation ofTrypanosoma cruzii infectionsin vitro andin vivo by transforming growth factor beta. J Exp Med 174:59, 1991

    Google Scholar 

  3. King CL, Mahanty S, Kumaraswami W, Abrams JS, Regunathan J, Jamarayan K, Ottesen EA, Nutman TB: Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J Clin Invest 92:1667–1673, 1993

    PubMed  Google Scholar 

  4. Barral-Netto M, Barrai A, Brownell LE, Skeiky YAW, Ellings-worth LR, Twardzik DR, Reed SG: Transforming growth factor-β in leishmania infection: An important parasite escape mechanism. Science 257:545–548, 1992

    PubMed  Google Scholar 

  5. de Kossodo S, Grau GE: Profiles of cytokine production in relation with susceptibility to cerebral malaria. J Immunol 151:4811–4820, 1993

    PubMed  Google Scholar 

  6. de Kossodo S, Grau GE: Role of cytokines and adhesion molecules in malaria immunopathology. Stem Cells Dayt 11:41–48, 1993

    PubMed  Google Scholar 

  7. Roberts AB, Sporn MB: The transforming growth factor-βs. Handb Exp Pharmacol 95(I):419–472

  8. Sporn MB, Roberts AB, Wakefield LM, de Crombrugghe B: Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol 105:1039–1045, 1991

    Google Scholar 

  9. Lebman DA, Lee FD, Coifman RL: Mechanism for transforming growth factorβ and IL-2 enhancement of IgA expression in lipopolysaccharide-stimulated B cell cultures. J Immunol 144:952–959, 1990

    PubMed  Google Scholar 

  10. Sonoda E, Matsumoto R, Hitoshi Y, Ishii, Sugimoto, Araki S, Tominaga A, Yamaguchi N, Takatsu: Transforming growth factorβ induces IgA production and acts additively with interleukin 5 for IgA production. J Exp Med 170:1415–1420, 1989

    PubMed  Google Scholar 

  11. Oswald IP, Cazzinelli RT, Sher A, James SL: IL-10 synergizes with IL-4 and transforming growth factors to inhibit macrophage cytotoxic activity. J Immunol 148:3578–3582, 1992

    PubMed  Google Scholar 

  12. Ding A, Nathan CF, Graycar J, Derynck R, Stuehr DJ, Srimal S: Macrophage deactivating factor and transforming growth factors-β1, -β2, and -β3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-γ. J Immunol 145:940–944, 1990

    PubMed  Google Scholar 

  13. Bogdan C, Nathan C: Modulation of macrophage function by transforming growth factor-β, interleukin-4, and interleukin-10. Ann NY Acad Sci 685:713–739, 1993

    PubMed  Google Scholar 

  14. Looareesuwan S, Kyle DE, Viravan C, Vanijanonta S, Wilairatana P: Treatment of patients with recrudescent malaria with a sequential combination of artesunate and mefloquine. Am J Trop Med 47:794–799, 1992

    Google Scholar 

  15. Harpa ZR, Edelmann R, Wassermann SS, Levine MM, Davis JR, Sztein MB: Serum cytokine profiles in experimental human malaria. J Clin Invest 90:515–523, 1993

    Google Scholar 

  16. Mshana RN, Boucandi J, Mshana NM, Mayombo J, Mendome G: Cytokines in the pathogenesis of malaria: Levels of IL-1, IL-4, IL-6, TNFα, and IFNγ in plasma of healthy individuals and malaria patients in a holoendemic area. J Clin Lab Immunol 34:313–139, 1991

    Google Scholar 

  17. Naotunne TDS, Karunaweera ND, Del Guidice G, Kularatne MU, Grau GE, Carter R, Mendis KN: Cytokines kill malaria parasites during infection crisis: Extracellular complementary factors are essential. J Exp Med 173:523–529, 1991

    PubMed  Google Scholar 

  18. Schafield L, Ferreira A, Nussenzweig V, Nussenzweig RS: Antimalarial activity of TNF and IFNα and IFNγ. Fed Proc 46:760, 1987

    Google Scholar 

  19. Taverne J, Tavernier J, Fiers W, Playfair JHL: Recombinant tumour necrosis factor inhibits malaria parasitesin vivo but notin vitro. Clin Exp Immunol 64:1–4, 1987

    Google Scholar 

  20. Kumaratilake JM, Ferrante A, Rzepcyk KL: The role of T-lymphocytes in immunity toP. falciparum: Enhancement of neutrophil-mediated killing by lymphotoxin and IFN-γ: Comparisons with TNF parasite effects. J Immunol 146:762–767, 1991

    PubMed  Google Scholar 

  21. Orago ASSO, Facer CA: Cytotoxicity of human NK cell subsets forPlasmodium falciparum erythrocytic schizonts: Stimulation with cytokines and inhibition with neomycin. Clin Exp Immunol 86:22–29, 1991

    PubMed  Google Scholar 

  22. Kuranaweera ND, Carter R, Grau GB, Kwiatkowski D, del Giudice G, Mendis KN: Tumour necrosis-dependent killing effects during paroxysm in non-immunePlasmodium vivax malaria patients. Clin Exp Immunol 88:499–506, 1992

    PubMed  Google Scholar 

  23. Grau GE, Bieler G, Pointaire P, de Kossodo S, Tacchini-Lotier F, Kassalli P, Piquet P, Lambert PH: Significance of cytokine production and adhesion molecules in malaria immunopathology. Immunol Lett 25:189–194, 1990

    PubMed  Google Scholar 

  24. Orago ASS, Facer CA: Cytokine-induced inhibition ofPlasmodium falciparum erythrocytic growthin vitro. Clin Exp Immunol 91:287–294, 1993

    PubMed  Google Scholar 

  25. Ferreira A, Schofield L, Enea V, Schellekeus H, van der Meide P, Collins WE, Nussenzweig RS, Nussenzweig V: Inhibition of development of exo-erythrocytic forms of malaria parasites by interferon-γ. Science 232:881–884, 1986

    PubMed  Google Scholar 

  26. Graninger W, Thalhammer F, Hollenstein U, Zotter GM, Kremsner PG: Serum protein concentrations inPlasmodium falciparum malaria. Acta Trop 52:121–128, 1992

    PubMed  Google Scholar 

  27. Ho M, Webster HK, Looareesuwan S, Supanarnond W, Philips RE, Chanthavanich P, Warrell DA: Antigen-specific immunosuppression in human malaria due toPlasmodium falciparum. J Infect Dis 153:763–771, 1986

    PubMed  Google Scholar 

  28. Ho M, Webster HK, Green B, Looareesuwan S, Kongchareon S, White N: Defective production of and response to IL-2 in acute falciparum malaria. J Immunol 441:2755–2759, 1988

    Google Scholar 

  29. Kremsner PG, Zotter GM, Feldmeier H, Graninger W, Rocha RM, Jansen-Rosseck R, Bienzle U: Immune responses in patients during and afterPlasmodium falciparum infection. J Infect Dis 161:1025–1028, 1990

    PubMed  Google Scholar 

  30. Kremsner PG, Feldmeier H, Zotter GM, Jansen-Rosseck R, Graninger W, Rocha RM, Bienzle U: Immunological alterations in uncomplicatedPlasmodium falciparum malaria. Relationship between parasitemia and indicators of macrophage activation. Acta Trop 46:351–359, 1989

    PubMed  Google Scholar 

  31. Chizzolini C, Grau GE, Geinoz A, Schrijvers D: T-lymphocyte gamma interferon production induced byPlasmodium falciparum antigen is high in recently infected non-immune and low in immune subjects. Clin Exp Immunol 79:95–99, 1990

    PubMed  Google Scholar 

  32. Grau GE, Taylor TE, Molyneux ME, Wirima JJ, Vasalli P, Hommel M, Lambert PH: Tumor necrosis factor and disease severity in children withPlasmodium falciparum malaria. N Engl J Med 320:1586–1591, 1989

    PubMed  Google Scholar 

  33. Kern P, Hemmer CJ, Van Damme J, Gruss HS, Dietrich M: Elevated tumor necrosis factor and interleukin-6 serum levels as markers for complicatedPlasmodium falciparum malaria. Am J Med 87:139–143, 1989

    PubMed  Google Scholar 

  34. Grau GE, Heremans H, Piquet PF, Pointaire P, Allet B, Lambert PH, Billian A, Vassalli P: Monoclonal antibody against interferon can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor. Proc Natl Acad Sci USA 86:5572–5574, 1989

    PubMed  Google Scholar 

  35. Kviatkowski D, Hill AUS, Sambon I, Twumasi P, Castracane J, Manoque KR, Erami A, Brewster DR, Greenwood BM: TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicatedPlasmodium falciparum malaria. Lancet 336:1201–1204, 1990

    PubMed  Google Scholar 

  36. Flynn RM, Paliadino MA: TNF and TGF-beta: The opposite sides of the avenue. Tumor Necrosis Factors 131, 1992

Download references

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Internal Medicine I, University Hospital of Vienna, Austria

    C. Wenisch, B. Parschalk, H. Burgmann & W. Graninger

  2. Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

    S. Looareesuwan

Authors
  1. C. Wenisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Parschalk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Burgmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Looareesuwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W. Graninger
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wenisch, C., Parschalk, B., Burgmann, H. et al. Decreased serum levels of TGF-β in patients with acutePlasmodium falciparum malaria. J Clin Immunol 15, 69–73 (1995). https://doi.org/10.1007/BF01541734

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01541734

Key words

Search

Navigation