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 β1 (TGF-β1), and tumor necrosis factor a (TNF-α) 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-α 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-α 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-β 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.