Multiple derangements of cytokine homeostasis in mice infected with immunosuppressive retrovirus.
Altered production of various lymphokines is considered an important factor in retrovirus-induced immunosuppression. We have measured the production of interleukin 2 (IL-2), interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-beta 1), and tumor necrosis factor alpha (TNF-alpha) in splenocytes of retrovirus-infected NMRI mice. In Con A-stimulated splenocytes from mice infected with the acute transforming retrovirus Friend leukemia complex (FLC), TNF-alpha and IL-6 production was significantly suppressed. We compared cytokine production in infection with Friend-derived murine immunosuppressive virus (Fd-MIV), a low oncogenic retrovirus that induces a immunosuppression of a magnitude similar to that of FLC. In Fd-MIV infection, the ability of lymphoid cells to produce both IL-2 and TNF-alpha was suppressed. The suppression of these cytokines coincided with the suppression of the primary antibody response. In contrast to FLC infection, the production of IL-6 was elevated. Furthermore, increased production of TGF-beta was found in unstimulated splenocytes from Fd-MIV-infected mice. Infection with immunosuppressive retroviruses induces a complex derangement of T-cell cytokine homeostasis and the relative contributions of the various factors to the immunosuppressed state are difficult to assess at present.
Faxvaag
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Institute of Cancer Research, University of Trondheim, Norway.
Espevik
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Dalen
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D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005622:Friend murine leukemia virus; D006706:Homeostasis; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007942:Leukemia, Experimental / Q000276:immunology*; D051379:Mice; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha