Continuous endotoxin infusion suppresses rat spleen cell production of cytokines

Endotoxin, i.e., lipopolysaccharides, was continuously infused into rats at a nonlethal dose by means of an implanted osmotic pump for up to 2 weeks. The pump was connected to the jugular vein by a polyethylene catheter. Administration of endotoxin via the pump compromised the ability of spleen cells to produce the lymphokines interleukin 1 and tumor necrosis factor after stimulation in vitro with endotoxin. In addition, the ability of the spleen cells to produce alpha/beta-interferon in response to endotoxin in vitro was also examined, as was the capability of the spleen cells to produce gamma-interferon following stimulation with concanavalin A. Suppression of the expected interleukin 1 and tumor necrosis factor production by spleen cells from rats continuously infused with endotoxin was observed. There was also a moderate effect on interferon production, but this was much less. These results provide further findings indicating the unresponsiveness of spleen cells to lipopolysaccharides, as well as to a nonspecific plant mitogen, following continuous infusion of endotoxin into rats via an implanted osmotic pump. Additional studies are needed to determine the mechanisms involved in such suppression.