Influenza virus infection results in altered responses of human mononuclear leukocytes to mitogen and antigen stimulation. We have previously shown (1,2) that depression of such proliferative responses to alternate (nonviral) stimuli was due to decreased monocyte-macrophage accessory cell function, with lymphocyte responsiveness preserved. It has been unclear whether altered influenza virusinfected macrophage accessory cell function was due to (a) inadequate presentation of mitogens, for example, together with class II HLA determinants; (b) inadequate production of essential cofactors, notably IL-1; (c) production of inhibitory factors, such as IL-1 inhibitors; (d) direct cell-cell inhibition; or (e) a combination of such processes. The studies reported herein were undertaken to determine whether the macrophages produce Ik-I or IL-I inhibitors after exposure to the virus.In addition, production of IL-1 and IL-1 inhibitors by respiratory syncytial virus (RSV)l-exposed human macrophages was examined. In contrast to influenza virus, infections with RSV commonly recur, despite serological evidence of immunity of the individual and the lack of clear evidence of antigenic shift or drift of the virus (2-4). RSV infection of human mononuclear leukocytes also results in depressed proliferative responses (2), but RSV differs significantly in ability to induce production of macrophage-derived immunoregulatory factors, such as IFN (2, 5). Materials and MethodsCell Collection and Separation. Mononuclear leukocytes were obtained from the peripheral blood of healthy adult donors by Ficoll-Hypaque sedimentation, and purified monocyte-derived macrophages were obtained by 24-h adherence separation of the cells in plastic culture dishes, as described previously (1, 2). Such macrophage preparations consist of 93-97% monocytes-macrophages by strict criteria for differentiation (1, 6). Unless noted otherwise, macrophages were cultured at 37°C in Eagle's MEM supplemented with 4% FCS, Hepes buffer, and penicillin (100 U/ml).