Cyclosporin A inhibits the production of gamma interferon (IFNγ), but does not inhibit production of virus-induced IFNα/β

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The effect of cyclosporin A (CsA) on the production of gamma interferon (IFNγ) versus IFNα/β was studied using mouse and human lymphocytes and fibroblasts. Spleen cells from C57B1/6 mice produced low but significant levels (40–60 U/ml) of IFNγ after 2 to 3 days of culture with irradiated DBA spleen cells. The addition of CsA at concentrations as low as 0.1 μg/ml completely inhibited (<10 U/ml) IFNγ production in these cultures. High levels of IFNγ (170–1200 U/ml) were produced when either C57B1/6 spleen cells or Ficoll-Hypaque-purified human peripheral blood lymphocytes (PBL) were cultured with the T-cell mitogen staphylococcal enterotoxin A (SEA). The addition of CsA (0.1 μg/ml) to these cultures also completely inhibited (<10 U/ml) IFNγ production. This inhibition was shown not to be due to a change in the kinetics of IFNγ production or to a change in the amount of SEA required for stimulation. IFNγ production in SEA-stimulated mouse spleen cells was inhibited at 3 days of culture even when CsA was added at 24 or 48 hr postculture initiation. Thus, CsA inhibits IFNγ production even when early events associated with lymphocyte activation have been allowed to take place. In contrast to IFNγ production, IFNα/β production by Newcastle disease virus (NDV)-infected mouse and human lymphocytes or fibroblasts was not inhibited by the addition of CsA (1 μg/ ml). CsA also did not block the action of IFNγ or IFNα/β since addition of CsA (1 μg/ml) to reference IFN standards had no effect on their antiviral activity. Thus, CsA inhibits the production of IFNγ by T cells but appears to have no effect on the production of IFNα/β by virus-infected cells or on the antiviral action of already produced IFNγ and IFNα/β.