1887

Journal of General Virology header logo

Volume 78, Issue 10

Elevation of cytokines associated with the thrombocytopenia of equine infectious anaemia. Free

Abstract

Thrombocytopenia is a common finding in infection with equine infectious anaemia virus (EIAV), a lentivirus with some homology to human immunodeficiency virus (HIV). The thrombocytopenia of EIA, like that in some HIV patients, appears to have a multifactorial pathogenesis. To investigate the decreased platelet production seen in experimental EIA, the levels of three potential negative regulators of platelet production - tumour necrosis factor-α (TNF-α), transforming growth factor- (TGF-) and interferon-α (IFN-α) - were measured in serum and bone marrow of six severe combined immunodefi- cient (SCID) foals and ten immunocompetent EIAV- infected foals. Levels of cytokines in pre-infection foal sera and bone marrow were compared with levels observed during clinical EIA. Mean serum levels of TNF-α and IFN-α were significantly higher ( < 0·05) on days 4 to 0 of thrombocytopenia than before infection. Serum TGF- was significantly elevated on all days except day 1 of thrombocytopenia. Bone marrow TNF-α levels were significantly increased in infected foals just before clinical thrombocytopenia. TGF- activity was not different in pre-infection and pre-thrombocytopenia bone marrows, but levels of TGF- protein as determined by immunohistochemical staining were significantly higher in pre-thrombocytopenia bone marrow. IFN-α activity in bone marrow increased just before thrombocytopenia, but the difference was not significant at < 0·05. Serum TNF-α levels were 2–2·5 times higher in SCID foals on three of the days prior to thrombocytopenia than in immunocompetent foals. No significant differences were found between the levels in SCID and immunocompetent foals of serum and bone marrow TGF- or IFN-α at any of the times examined.

  • Published Online:
© Society for General Microbiology 1997
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-10-2541
1997-10-01
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/10/9349475.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-10-2541&mimeType=html&fmt=ahah

References

  1. Abbas P. K., Lichtman A. H., Pober J. S. 1991; Cytokines. In Cellular and Molecular Immunology pp 226–243 Wonsiewicz M. J. Edited by Philadelphia: W. B.Saunders Co;
     [Google Scholar]
  2. Allen J. B., Wong H. L., Guyre P. M., Simon G. L., Wahl S. M. 1991; Association of circulating receptor Fc gamma RIII-positive monocytes in AIDS patients with elevated levels of transforming growth factor-beta. Journal of Clinical Investigation 87:1773–1779
     [Google Scholar]
  3. Ballem P. J., Belzberg A., Devine D. V., Lyster D., Spruston B., Chambers H., Doubroff P., Mikulash K. 1992; the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. New England Journal of Medicine 327:1779–1784
     [Google Scholar]
  4. Banks K. L., McGuire T. C. 1975; Surface receptors on neutrophil and monocytes from immunodeficient foals. Immunology 28:581–588
     [Google Scholar]
  5. Blick M., Sherwin S. A., Rosenblum M., Gutterman J. 1987; Phase 1 study of recombinant tumor necrosis factor in cancer patients. Cancer Research 47:2986–2989
     [Google Scholar]
  6. Branch D. R., Shah A., Guilbert L. J. 1991; A specific and reliable bioassay for the detection of femtomolar levels of human and murine tumor necrosis factors. Journal of Immunological Methods 143:251–261
     [Google Scholar]
  7. Bull B. S., Schneiderman M. A., Brecher G. 1965; Platelet counts with the Coulter Counter. American Journal of Clinical Pathology 44:678–688
     [Google Scholar]
  8. Carlo-Stella C., Cazzola M., Ganser A., Bergamashi G., Pedrazzoli P., Hoelzer D., Ascari E. 1988; Synergistic antiproliferative effect of recombinant interferon-gamma with recombinant interferon-alpha on chronic myelogenous leukemia hematopoietic progenitor cells (CFU- GEMM, CFU-MK, BFU-E, and CFU-GM). Blood 72:1293–1299
     [Google Scholar]
  9. Chuncharunee S., Carter C. D., Studtmann K. E., Caro J., Coffey R. J., Dessypris E. N. 1993; Chronic administration of transforming growth factor-beta suppresses erythropoietin-dependent erythropoiesis and induces tumour necrosis factor in vivo. British Journal of Haematology 84:374–380
     [Google Scholar]
  10. Clabough D. L., Gebhard D., Flaherty M. T., Whetter L. E., Perry S. T., Coggins L., Fuller F. J. 1991; Immune-mediated thrombocytopenia in horses infected with equine infectious anemia virus. Journal of Virology 65:6242–6251
     [Google Scholar]
  11. Crawford T. B., Wardrop K. J., Tornquist S. J., Reilich E., Meyers K. M., McGuire T. C. 1996; A primary production deficit in the thrombocytopenia of equine infectious anemia. Journal of Virology 70:7842–7850
     [Google Scholar]
  12. Ganser A., Carlo-Stella C., Greher J., Volkers B., Hoelzer D. 1987; Effect of recombinant interferons alpha and gamma on human bone marrow-derived megakaryocytic progenitor cells. Blood 70:1173–1179
     [Google Scholar]
  13. Geissler R. G., Ottmann O. G., Eder M., Kojouharoff G., Hoelzer D., Ganser A. 1991; Effect of recombinant human transforming growth factor beta and tumor necrosis factor alpha on bone marrow progenitor cells of HIV-infected persons. Annals of Hematology 62:151–155
     [Google Scholar]
  14. Gugliotta L., Bagnara G. P., Catani L., Gaggioli L., Gurini A., Zauli G., Belmonte M. M., Lauria F., Macchi S., Tura S. 1989; In vivo and in vitro inhibitory effect of alpha-interferon on megakaryocyte colony growth on essential thrombocythaemia. British Journal of Haematology 71:177–181
     [Google Scholar]
  15. Hunter C. A., Abrams J. S., Beaman M. H., Remington J. S. 1993; Cytokine mRNA in the central nervous system of SCID mice infected with Toxoplasma gondii : importance of T-cell independent regulation of resistance to T. gondii. Infection and Immunity 61:4038–4044
     [Google Scholar]
  16. Ishibashi T., Miller S. L., Burstein S. A. 1987; Type-beta transforming growth factor is a potent inhibitor of murine megakaryo- cytopoiesis in vitro. Blood 69:1737–1741
     [Google Scholar]
  17. Jacobsen S. E. W., Ruscetti F. W., Roberts A. B., Keller J. R. 1993; TGF-beta is a bidirectional modulator of cytokine receptor expression on murine bone marrow cells. Journal of Immunology 151:4534–4544
     [Google Scholar]
  18. Jandl J. H. 1987; Disorders of platelets. In Textbook of Hematology, 1st edn. pp 1041–1095 Boston: Little, Brown & Co;
     [Google Scholar]
  19. Johnson R. A., Waddelow T. A., Caro J., Oliff A., Roodman G. D. 1989; Chronic exposure to tumor necrosis factor in vivo preferentially inhibits erythropoiesis in nude mice. Blood 74:130–138
     [Google Scholar]
  20. Karpatkin S., Nardi M., Lennette E. T. 1988; Anti-human immunodeficiency virus type 1 antibody complexes on platelets of seropositive thrombocytopenic homosexuals and narcotic addicts. Proceedings of the National Academy of Sciences USA: 859763–9767
     [Google Scholar]
  21. Lehmann R., Joller H., Haagmans B. L., Lutz H. 1992; Tumor necrosis factor alpha levels in cats experimentally infected with feline immunodeficiency virus: effects of immunization and feline leukemia virus infection. Veterinary Immunology and Immunopathology 35:61–69
     [Google Scholar]
  22. Ley K. D., Burger D., McGuire T., Henson J. B. 1970; Equine interferon: absence in equine infectious anemia and kinetics of induction in equine cells. Journal of Infectious Diseases 122:10–15
     [Google Scholar]
  23. Linderholm M., Ahlm C., Settergren B., Waage A., Tärnvik A. 1996; Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6 and IL-10 in patients with hemorrhagic fever with renal syndrome. Journal of Infectious Diseases 173:38–43
     [Google Scholar]
  24. Louache F., Bettaieb A., Henri A., Oksenhendler E., Farcet J., Bierling P., Seligmann M., Vainchenker W. 1991; Infection of megakaryocytes by human immunodeficiency virus in seropositive patients with immune thrombocytopenic purpura. Blood 78:1697–1705
     [Google Scholar]
  25. Maciejewski J. P., Weichold F. F., Young N. S. 1994; HIV-1 suppression ofhematopoiesis in vitro mediated by envelope glycoprotein and TNF-alpha. Journal of Immunology 153:4303–4310
     [Google Scholar]
  26. Maury C. P. J., Lahdevirta J. 1990; Correlation of serum cytokine levels with haematological abnormalities in human immunodeficiency virus infection. Journal of Internal Medicine 227:253–257
     [Google Scholar]
  27. Ott L. 1988 An Introduction to Statistical Methods and Data Analysis, 3rd edn. Boston: PWS-Kent;
     [Google Scholar]
  28. Perryman L. E., , McGuire T. C., Crawford T. B. 1978; Maintenance of foals with combined immunodeficiency: causes and control of secondary infections. American Journal of Veterinary Research 39:1043–1047
     [Google Scholar]
  29. Perryman L. E., O’Rourke K. I., McGuire T. C. 1988; Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection. Journal of Virology 62:3073–3076
     [Google Scholar]
  30. Sherman M. L., Spriggs D. R., Arthur K. A., Imamura K., Frei E., Kufe D. W. 1988; Recombinant human tumor necrosis factor administered as a five-day continuous infusion in cancer patients: phase I toxicity and effects on lipid metabolism. Journal of Clinical Oncology 6:344–350
     [Google Scholar]
  31. Steinberg H. N., Crumacker C. S., Chatis P. A. 1991; In-vitro suppression of normal human bone marrow progenitor cells by human immunodeficiency virus. Journal of Virology 65:1765–1769
     [Google Scholar]
  32. Stephens R. M., Casey J. W., Rice N. R. 1986; Equine infectious anemia virus gag and pol genes: relatedness of visna and AIDS virus. Science 231:589–594
     [Google Scholar]
  33. Su H. C., Ishikawa R., Biron C. A. 1993; Transforming growth factor-beta expression and natural killer cell responses during virus infection of normal, nude, and SCID mice. Journal of Immunology 151:4874–4890
     [Google Scholar]
  34. Tizard I. R. 1995; Interferons. In Cytokines in Animal Health and Disease pp 1–57 Myers M. J., Murtagh M. P. Edited by New York: Marcel Dekker;
     [Google Scholar]
  35. Tornquist S. J., Crawford T. B. 1997; Suppression of megakaryocyte colony growth by plasma from foals infected with equine infectious anemia virus. Blood in press.
    [Google Scholar]
  36. Tornquist S. J., Oaks J. L., Crawford T. B. 1996; The role of TNF α and TGF-β in suppression of megakaryocytopoiesis in equine infectious anemia. Abstract. Veterinary Pathology 33:576
     [Google Scholar]
  37. Torre D., Zeroli C., Giola M., Ferrario G., Fiori G. P., Bonetta G., Tambini R. 1994; Serum levels of interleukin-1 alpha, interleukin-1 beta, interleukin-6 and tumor necrosis factor in patients with acute viral hepatitis. Clinical Infectious Disease 18:194–198
     [Google Scholar]
  38. Von Sydow M., Sonnerborg A., Gaines H., Stranneard O. 1991; Interferon-alpha and tumor necrosis factor-alpha in serum of patients in various stages of HIV-1 infection. AIDS Research and Human Retroviruses 7:375–380
     [Google Scholar]
  39. Wadenvik H., Kutti J., Ridell B., Revesz P., Jacobsson S., Magunsson B., Westine J., Vilen L. 1991; The effect of alphainterferon on bone marrow megakaryocytes and platelet production rate in essential thrombocythemia. Blood 77:2103–2108
     [Google Scholar]
  40. Wardrop K. J., Baszler T. V., Reilich E. 1996; A morphometric study of bone marrow megakaryocytes in foals infected with equine infectious anemia virus. Veterinary Pathology 33:222–227
     [Google Scholar]
  41. Yilma T., Perryman L. E., McGuire T. C. 1982; Deficiency of interferon-gamma but not interferon-beta in Arabian foals with severe combined immunodeficiency. Journal of Immunology 129:931–933
     [Google Scholar]
  42. Young N., Mortimer P. 1984; Viruses and bone marrow failure. Blood 63:729–737
     [Google Scholar]
  43. Zauli G., Davis B. R., Re M. C., Visani G., Furlini G., Placa M. L. 1992; Tat protein stimulates production of transforming growth factor-beta 1 by marrow macrophages : a potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression. Blood 80:3036–3043
     [Google Scholar]
  44. Zucker-Franklin D. 1994; The effect of viral infections on platelets and megakaryocytes. Seminars in Hematology 31:329–337
     [Google Scholar]
  45. Zucker-Franklin D., Cao Y. 1989; Megakaryocytes of human immunodeficiency virus-infected individuals express viral RNA. Proceedings of the National Academy of Sciences USA: 865595–5599
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-78-10-2541
Loading
Elevation of cytokines associated with the thrombocytopenia of equine infectious anaemia.
J. Gen. Virol. 78, 2541 (1997); https://doi.org/10.1099/0022-1317-78-10-2541
/content/journal/jgv/10.1099/0022-1317-78-10-2541
/content/journal/jgv/10.1099/0022-1317-78-10-2541
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error