Remote effects of inflammation on non-specific immunity.

Following inflammation induced in mice with non-biodegradable, non-diffusible, and non-antigenic substances, host resistance is increased against bacteria, parasites and malignant cells injected at a distance from the inflammatory focus. This resistance is also increased in germ-free and nude mice. The increased resistance is correlated with (1) an increased leukopoiesis induced, at least in part, by a protein (MW = 40 kDa, pI = 5.2) which, in vitro, is able to induce the differentiation of bone-marrow cells into polymorphs; (2) the occurrence of giant cells in the granuloma which, after incubation in vitro, release an immunostimulating protein able to activate mice macrophages in vivo; (3) activation in vivo of liver and spleen macrophages following the occurrence, both in granuloma and in serum, of a protein (MW = 56 kDa, pI = 5) which, contrary to endotoxin, is heat-labile and can fully protect mice against Listeria monocytogenes. Furthermore, this protein, which is different from TNF and GM CSF, is able to activate macrophages against Lewis tumor cells. The same protein can be isolated from rat and is antigenically related to a human protein having the same biological activity.