THERMAL INJURY-INDUCED IMMUNOSUPPRESSION IN MICE - THE ROLE OF MACROPHAGE-DERIVED REACTIVE NITROGEN INTERMEDIATES

Macrophages (M phi) have been implicated in the suppression of lymphoc yte function following thermal injury. Splenocytes isolated from C57BL /6NCR female mice 4-7 days after thermal injury displayed suppressed p roliferative responses to Concanavalin A (ConA) and Lipopolysaccharide (LPS) and high levels of reactive nitrogen intermediate (RNI) product ion. Inhibition of nitric oxide synthase activity with NG-monomethyl-L -arginine restored ConA responses but not LPS responses. Surprisingly, ConA-stimulated interferon-gamma (IFN-gamma) production was increased in splenocytes from injured mice. IFN-gamma contributed to the RNI-me diated immunosuppression as antibodies against IFN-gamma reduced RNI p roduction and immunosuppression. ConA-stimulated co-cultures of spleni c M phi fi om injured mice and normal splenocytes produced high levels of RNI only under conditions of cellular contact and splenic m phi fr om injured mice were capable of suppressing normal splenocytes respons es in co-culture. These results indicate that M phi activity and speci fically RNI production contribute to the suppression of T lymphocyte f unction after thermal injury.