Counteracting effect of interferon-alpha and -beta on interferon- gamma-induced production of nitric oxide which is suppressive for antibody response.
We investigated the nitric oxide (NO)-mediated immunosuppressive activity of macrophages and the regulatory effect of type I (alpha and beta) interferons (IFNs) on IFN-gamma-induced NO production by macrophages. In the sheep red blood cell (SRBC)-specific secondary antibody response in vitro, the addition of macrophages to the culture of primed spleen cells substantially decreased the number of plaque-forming cells. The concentration of nitrite in the culture supernatant showed a positive correlation with the number of macrophages added in a dose- dependent manner, and the addition of NMMA, a potent inhibitor of NO production, resulted in the restoration of of the response. In addition, anti-IFN-gamma antibody abolished the ability of the immune culture supernatant to stimulate macrophages to produce NO. Therefore, the macrophage-dependent immunosuppression was due primarily to NO that was produced by macrophages in response to IFN-gamma derived from responding lymphocytes. The pretreatment of macrophages with IFN-alpha or -beta gave rise to a dramatic reduction of IFN-gamma-mediated NO production. In addition, the suppressive activity of these macrophages was much lower than that of untreated macrophages. These results indicate that type I IFNs can regulate the immune response by modulating IFN-gamma-induced production of immunosuppressive NO.
Deguchi
M
M
Department of Zoology, Faculty of Science, Kyoto University, Japan.
Inaba
K
K
Muramatsu
S
S
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D005260:Female; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D007370:Interferon Type I / Q000502:physiology*; D016898:Interferon-alpha / Q000502:physiology; D016899:Interferon-beta / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology
D007166:Immunosuppressive Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D009569:Nitric Oxide; D016899:Interferon-beta; D007371:Interferon-gamma