Modulation by immunosuppressive agents of peripheral blood mononuclear cell responses to influenza A virus

The response to influenza A virus of peripheral blood mononuclear cells (PBMC) isolated from normal healthy adults was studied by measuring antigen-specific lymphocyte proliferation and interferon and interleukin-2 production by these cells in vitro. Under various experimental conditions, methylprednisolone, doxorubicin, vincristine, and vinblastine each reduced lymphocyte proliferation of the PBMC exposed to influenza A virus antigen. Treatment of cells with these drugs did not reduce expression of influenza A virus antigens by PBMC as detected by flow cytometry and did not reduce cell viability. In vitro treatment of the cells with methylprednisolone and doxorubicin reduced interferon and interleukin-2 yields. Experimental conditions necessary to reduce lymphokine yields varied with the immunosuppressive drug tested. Vincristine and vinblastine treatment of the cells did not reduce interferon or interleukin-2 yields. We conclude that methylprednisolone and doxorubicin at clinically achievable concentrations significantly affected the response of PBMC to influenza A virus in vitro. The effects of these immunosuppressive agents on lymphokine production were different from those reported in previous studies in which mitogens and Newcastle disease virus were used as inducers. The sensitivity of PBMC to these immunosuppressive agents is clearly related to the inducing agent used.