Thermal injury-induced immunosuppression in mice: the role of macrophage-derived reactive nitrogen intermediates

Macrophages (M phi) have been implicated in the suppression of lymphocyte function following thermal injury. Splenocytes isolated from C57BL/6NCR female mice 4-7 days after thermal injury displayed suppressed proliferative responses to Concanavalin A (ConA) and Lipopolysaccharide (LPS) and high levels of reactive nitrogen intermediate (RNI) production. 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-mediated immunosuppression as antibodies against IFN-gamma reduced RNI production and immunosuppression. ConA-stimulated co-cultures of splenic M phi fi om injured mice and normal splenocytes produced high levels of RNI only under conditions of cellular contact and splenic m phi from injured mice were capable of suppressing normal splenocytes responses in co-culture. These results indicate that M phi activity and specifically RNI production contribute to the suppression of T lymphocyte function after thermal injury.