The immunosuppressive effects of the in vivo administration of endotoxin as influenced by macrophages.

It is well documented that endotoxin can have immunosuppressive effects on lymphocytes and induce the production and secretion of monokines which act on the lymphocytes. To delineate the interaction between macrophages and lymphocytes more clearly, 0.15 mg of lipopolysaccharide (LPS) (E. coli 0111:B4) was injected into Hartley guinea pigs intraperitoneally twice a day for 7 days (saline for control group). Seven days after the last injection, spleens were taken and lymphocyte proliferation was determined in the presence and absence of macrophages. When macrophages were present, there was a significant suppression of lymphocyte proliferation when PHA and PWM were used as mitogens. There was no suppression of proliferation when the macrophages were removed. Splenic macrophages were also cultured in the presence and absence of LPS and their supernatants analyzed for PGE2 and TXB2. There was no significant difference between the endotoxin and control groups for PGE2 or TXB2 production in the presence and absence of LPS. However, the endotoxin group had significant decreases in serum levels of C3 postinjection of endotoxin which could indicate C3 degradation by LPS. Taken together these results give further evidence that macrophage products in addition to PGE2 can inhibit lymphocyte proliferation. C3 degradation products could possibly stimulate macrophages to produce inhibitors of lymphocyte proliferation or induce suppressor cells.