Interleukin 1 and interleukin 1 inhibitor production by human macrophages exposed to influenza virus or respiratory syncytial virus. Respiratory syncytial virus is a potent inducer of inhibitor activity.

Abstract

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).

Animal Models of Respiratory Syncytial Virus Pathogenesis and Vaccine Development: Opportunities and Future Directions

“…During the CTL response to HRSV, approximately half of HRSV-specific CD8 + T cells in the lungs of BALB/c mice produce IFN-, compared to influenza virus infection where nearly all influenza-specific CD8 + T cells in the lung are IFN- + (Chang and Braciale, 2002). These data are in agreement with HRSV suppression of T cell proliferation in vitro (Preston et al, 1992(Preston et al, , 1995Roberts et al, 1986). HRSV inhibition of T cell responses may be an important reason why HRSV does not confer adequate immunity.…”

Bacterial cell wall-induced immunosuppression. Role of transforming growth factor beta.

“…Activated macrophages have frequently been associated with various forms of immunodeficiency, and a number of macrophage-derived suppressor molecules have been reported including prostaglandins (19), reactive oxygen intermediates (20), and a variety of uncharacterized factors produced in response to virus, mycobacteria, and other stimuli (29)(30)(31)(32)(33). The peptidoglycan-polysaccharide polymers of SCW stimulate human (Allen et al ., manuscript in preparation) and rat (Feldman et al .…”

Virulent Avian Influenza A Viruses: Their Effect on Avian Lymphocytes and Macrophages in vivo and in vitro

“…that infected macrophages release soluble factors that activate adjacent lymphocytes and enhance their ability to respond to mitogen. In support of this, human macrophages produce intedeukin-I (Roberts et aL, 1986) in response to influenza A virus; therefore avian macrophages may produce interleukin-1 and other cytokines in response to Ty/Ont. Direct activation of lymphocytes by Ty/Ont cannot be excluded since they appear to be infected by the virus; however, studies by Roberts (1982) suggest that effects of influenza A viruses on lymphocyte proliferation are macrophage-dependent.…”