The influence of host health and environment on natural cytotoxicity of mouse macrophages

The health and environment of the host influence the 'natural cytotoxicity' of mouse peritoneal macrophages against tumor targets in vitro. In these studies, we have used mice derived by hysterectomy and maintained under barrier conditions. Peritoneal macrophages harvested from untreated mice and from those that received IP injections of thioglycollate broth, bactopeptone, or soluble concanavalin A were not cytotoxic to tumor targets in vitro. Resident and various inflammatory macrophages responded alike to activation by lipopolysaccharide or macrophage-activating factor. Macrophages were rendered tumoricidal following inflammation and/or infection of the host or imposition of stressful conditions on the host. Inflammation was induced by SC injection of complete Freund's adjuvant or IP injection of Mycobacterium bovis organism into the mice. Stress was induced by crowding the mice. Macrophages obtained from mice stressed for 2 weeks by crowding were spontaneously cytotoxic to tumor targets in vitro. Moreover, macrophages obtained from mice that fought among themselves and developed skin wounds were highly tumoricidal in vitro. These data demonstrate that environmental conditions influence the activation of tumoricidal properties of macrophages in apparently healthy donors.