Inflammation and host resistance against pathogens.

Abstract

After a review of all factors released in an inflammatory focus which act on pathogens, a summary of recent findings concerning the influence of an inflammation on the remote control of mouse resistance against pathogens is given. In treated mice, the ability of spleen and liver macrophages to killListeria was found to be increased between 3 and 18 days following the induction of the inflammation. An increased resistance against the Lewis carcinoma was found, even when the mice were treated one day after the inoculation of malignant cells. In the treated mice, an increased cellular multiplication was observed in bone marrow, thymus, spleen, lymph nodes whereas no variations were observed in other tissues. The higher host resistance is correlated with an increased leucopoiesis and the activation of liver and spleen macrophages. The serum of treated animals is ablein vitro to activate peritoneal macrophages against Lewis carcinoma cells, to stimulate the multiplication of bone marrow cells and to agglutinate malignant cells. In order to explain the mechanisms of such an increased host resistance, investigations were undertaken to isolate and characterize possible active substances in the granuloma and in the serum from granuloma-bearing mice, and to check the possible activity of mediators of inflammatory reactions. Concerning the granuloma and the serum, it was possible, following electrofocusing, to extract and to isolate a fraction which is able to protect mice against a lethal inoculum ofListeria. Among the known mediators of acute inflammation, it was found not only that kinins are able to increase the spreading of macrophagesin vitro but that kinins or some of their degradation products are able,in vivo, to increase the resistance of mice againstListeria and the Lewis carcinoma. These results emphasize the importance of local non-specific inflammatory reactions on macrophages.