Biotherapy

, Volume 1, Issue 3, pp 227–231 | Cite as

Thein vivo andin vitro effects of interleukin-1 and tumor necrosis factor on murine cytomegalovirus infection

  • Jos W. M. van der Meer
  • Robert H. Rubin
  • Mark Pasternack
  • Donald N. Medearis
  • Patricia Lynch
  • Charles A. Dinarello
Article

Abstract

The effects of tumor necrosis factor (TNF) and interleukin-1 (IL-1) on infection with murine cytomegalovirus (MCMV) were investigatedin vitro andin vivo. The addition of each of these cytokines (at 1 ng/ml) to tissue culture monolayers 24 hr prior to MCMV challenge produced a reproducible decrease in vital titer (from 1 × 108 pfu to approximately 4 × 106 pfu for both cytokines). There was no further increase in this effect when a 10 or 100 ng/ml of each of these cytokines was employed. Despite thesein vitro effects, the pretreatment of suckling, weanling, or adult mice with 80 or 400 ng of TNF or IL-1 alone, or 80 ng of each cytokine together, had no effect on the survival of mice following MCMV. Similarly, neither of these cytokines adversely influenced the protective effects of hyperimmune anti-MCMV antiserum; that is, they did not attenuate the protection conferred by the antiserum nor affect the protective effects of subtherapeutic doses of the antiserum. We conclude that despite promising antiviral effects against MCMVin vitro, these agents do not result in a useful therapeutic effectin vivo. Moreover, despite the ability of IL-1 to induce ACTH and corticosterone in mice, IL-1 treatment did not increase the mortality to CMV.

References

  1. 1.
    Dinarello CA. 1988. Interleukin-1. FASEB Journal 2(2): 108–15.Google Scholar
  2. 2.
    Beutler B, Cerami A. 1987. Cachectin; more than a tumor necrosis factor. New Engl J Med 316: 379–85.Google Scholar
  3. 3.
    Van der Meer JWM, Barza M, Wolff SM, Dinarello CA. 1988. Low dose recombinant interleukin-1 protects granulocytopenic mice from lethal gram-negative infection. Proc Natl Acad Sci USA 85: 1620–3.Google Scholar
  4. 4.
    Van't Wout JW, van der Meer JWM, Barza M, Dinarello CA. Protection of neutorpenic mice from lethalCandida albicans infection by recombinant interleukin-1. Eur J Immunol 18: 1143–46Google Scholar
  5. 5.
    Ozaki Y, Ohashi T, Minami A, Nakamura SI. 1987. Enhanced resistance of mice to bacterial infection induced by recombinant human interleukin-la. Infect Immun 55: 1436–40.Google Scholar
  6. 6.
    Van der Meer JWM. 1988. The effects of recombinant interleukin-1 and recombinant necrosis factor on non-specific resistance to infection. Biotherapy 1: 19–25.Google Scholar
  7. 7.
    Parant M, Parant F, Vinit MA, Chedid L. 1987. Action protectrice du “tumor necrosis factor” (TNF) obtenu par recombinaison genetique conter l'infection experimentale bacterienne ou fongique. C. R. Acad Sc Paris 304: III, 1–4.Google Scholar
  8. 8.
    Wong GHW, Goeddel DV. 1986. Tumor necrosis factors alpha and beta inhibit virus replication and synergise with interferons. Nature, 323: 819–22.Google Scholar
  9. 9.
    Mestan J, Digel W. Mittnacht S, Hillen H, Blohm D, Moller A, Jacobsen H, Kirchner H. 1986. Antiviral effects of recombinant tumor necrosis factor in vitro. Nature 323: 816–19.Google Scholar
  10. 10.
    Koff WC, Fann AV. 1986. Human tumor necrosis factor alpha kills herpesvirus infected but not normal cells. Lymphokine res 5: 215–21.Google Scholar
  11. 11.
    Ito M, O'Malley JA. 1987. Antiviral effects of recombinant human tumor necrosis factor. Lymphokine res 6: 309–18.Google Scholar
  12. 12.
    Wong GH, Krowka JF, Stites DP, Goeddel DV. 1988. In vitro anti human immunodeficiency virus activities of tumor necrosis factor alpha and interferon gamma. J Immunol 140: 120–4, 1988.Google Scholar
  13. 13.
    Bielefeldt-Obmann H, Babiuk LA. 1988. Influence of interferons alpha and gamma and of tumor necrosis factor on persistent infection with bovine viral diarrhoea virus in vitro. J Gen Virol 69: 1399–1403.Google Scholar
  14. 14.
    Arakawa T, Hsu YR, Toth E, Stebbing N. 1987. The antiviral activity of human tumor necrosis factor alpha. J Interferon Res 7: 103–5.Google Scholar
  15. 15.
    Van Damme J, De Ley M, Van Snick J, Dinarello CA, Billiau A. 1987. The role of interferon-B1 and the 26-kDa protein (interferon-B2) as mediators of the antiviral effect of interleukin 1 and tumor necrosis factor. J Immunol 139: 1867–72.Google Scholar
  16. 16.
    Rubin RH. 1988. Infection in the renal and liver transplant patient. p. 559–621. In, Rubin RH, Young LS (eds): Clinical Approach to Infection in the Compromised Host. 2nd edition. Plenum Medical Book Co, New York.Google Scholar
  17. 17.
    Rubin RH, Wilson EJ, Barrett LV, Medearis DN. 1984. Primary cytomegalovirus infection following cardiac transplanation in a murine model. Transplanation 37: 306–10.Google Scholar
  18. 18.
    Selgrade MK, Osborne JE. 1974. Role of macrophages in resistance to murine cytomegalovirus. Infect Immunity 10: 1383–90.Google Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Jos W. M. van der Meer
    • 1
  • Robert H. Rubin
    • 1
  • Mark Pasternack
    • 1
  • Donald N. Medearis
    • 1
  • Patricia Lynch
    • 1
  • Charles A. Dinarello
    • 1
  1. 1.Dept. Internal MedicineUniversity HospitalNijmegenThe Netherlands
  2. 2.Infectious Disease UnitMassachusetts General HospitalBoston

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