In vivo effects of cyclosporine on influenza A virus-infected mice.

Cyclosporine (cyclosporin A, CsA) administered to mice substantially affects their immune response to an influenza A virus infection. If treated with CsA for 21 days, the mouse lungs contain high titers of virus which are cleared more slowly than in controls. Indicators of pathological damage--lung weight, extent of consolidation, fine morphology, and the extent of infiltration of dividing cells into the lung--showed that administration of CsA greatly decreased the level of inflammation. The production of hemagglutination-inhibiting (HI) antibody was delayed but reached almost control levels and NK cell activity in the lung was also comparable to control levels. In contrast, a delayed-type hypersensitivity (DTH) response to the virus could not be elicited in the CsA-treated, infected mice at 6 or 12 days after infection. Cytotoxic-T-cell (Tc-cell) activity was present in the lungs of such mice though its appearance was delayed and the activity recovered was less than that of the control infected mice. If administered with a dose of virus lethal for normal mice. CSA-treated mice survived, probably due to the greatly reduced level of immunopathological damage in the infected lung.