LIPOPOLYSACCHARIDE, TUMOR-NECROSIS-FACTOR, AND INTERLEUKIN-1 INTERACT TO CAUSE HYPOTENSION

Lipopolysaccharide (LPS) causes the syndrome of septic shock by initiating the release of endogenous mediators such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) from macrophages. Hypotension is one of the important clinical features of septic shock; however, TNF is only hypotensive in high doses. Therefore we have investigated the interactions of low, nonhypotensive doses of LPS, IL-1, and TNF in the restrained unanesthetized rabbit. Combinations of nonhypotensive doses of TNF, IL-1, and LPS produced significant (p < 0.05) decreases in blood pressure as compared with doses of each of the substances alone. TNF bioactivity in animals that were made hypotensive with combinations of TNF, IL-1, and LPS was lower than in animals that were made hypotensive with TNF alone. This suggests that TNF release that is stimulated by LPS is not the sole cause of the hypotension that is seen in this model of endotoxic shock. In this model, interactions of LPS, IL-1, and TNF occur and may explain hypotension during some episodes of sepsis.