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We determined the effect of thermal injury on the in vitro production of the immunoactive substances tumor necrosis factor, interleukin 1, prostaglandin E2, and complement component C3 by lipopolysaccharide-stimulated guinea pig bone marrow macrophages and on the cytotoxicity of these cells. Macrophages from burned animals produced different amounts of these mediators compared with unburned animals at certain culture times, suggesting that thermal injury could program the bone marrow cells to respond differently from normal cells to in vitro stimulation with lipopolysaccharide. Also, the macrophages from burned animals displayed greater cytotoxicity towards L929 target cells. These results suggest that there is a complex interaction among cellular secretory products, especially after thermal injury, that may be important in host defense.

The release of C3 under various conditions by cultured monocytes/macrophages isolated from burned, trauma, and septic trauma patients was determined. When monocytes were cultured for up to 14 days there was no difference in production and release of C3 by normals and patients; C3 production rose slowly at first then rose rapidly from 8-14 days of culture. C3 production continued for up to 28 days of culture. When lymphocytes were present with the monocytes for the first 24 hr of culture there were differences in C3 production by normal and patient cells at various times of culture. There were differences in C3 release by patients' 24 hour-cultured cells at certain postburn and injury days. Macrophages from burned patients released less C3 than normal cells and macrophages from septic trauma patients released more C3 than normal cells.

The synthesis and release of C3, PGE2, and TxB2 by cultured splenic, alveolar and peritoneal guinea pig macrophages in 24 hour culture was determined. There were significant differences in C3 production among all three sources of macrophages. Splenic macrophages produced significantly less PGE2 than alveolar or peritoneal macrophages. Peritoneal macrophages produced significantly more TxB2 than splenic or alveolar macrophages. The cells from the different sources appear to be different populations of macrophages.

Serum levels of properdin, Factor B and C3 and the ability of these sera to opsonize E. coli 075 were measured in 17 patients with surgical infections ranging in severity from mild to fatal. There was good direct correlation between severity of infection, serum levels of properdin and C3, and the ability of the serum to support opsonization. The levels of Factor B were not significantly reduced when measured by radial immunodiffusion, but immunoelectrophoresis showed conversion. Restoration of full opsonic activity was accomplished only by the addition of a combination of C3, Factor B, and properdin in excess. The findings provide evidence that severe bacterial infection causes a consumption of opsonic proteins which may result in a reduced ability of the patient's serum to opsonize bacteria and thereby further increase susceptibility to infection.