The effect of cyclosporine on macrophage oxidative burst potential during graft-versus-host reactions in mice

The development of graft-versus-host reactions in mice was characterized by an increase in activated macrophage populations in the peritoneum and spleen of the animals. In the present study we tested the effect of the immunosuppressive agent CsA on the appearance and activity of such macrophages. Parental spleen lymphocytes were injected intraperitoneally into F1 hybrids (BALB/c x C57Bl/6), and 13 days following injection we monitored the number of peritoneal exudate cells (PEC), spleen enlargement, and the oxidative burst (OB) of adherent peritoneal macrophages (APM). Macrophage OB was assessed by measuring O2- and H2O2 production, following stimulation with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). In GVHR mice a 72% increase in their spleen to body weight ratio was observed, whereas in CsA-treated GVHR mice only a 32% increase was evident. Assessment of the effect of CsA on the number and function of peritoneal cells revealed that CsA caused a 73% reduction in the number of infiltrating PEC in GVHR mice. Furthermore, measurements of H2O2 and O2- production by APM revealed that the overall OB capacity of APM from CsA-treated mice was significantly reduced compared to APM from nontreated GVHR mice. CsA had no effect on the number and OB activity of paraffin oil elicited or resident PEC. These results indicate that CsA may prevent recall and activation of macrophages via its effect on T cell lymphokine release and thus may lessen the contribution of macrophage-derived toxic reagents to the damage inflicted by GVHR.