PARALLEL RELATIONSHIP BETWEEN THE INCREASE IN SEROTONIN IN THE LIVER AND THE HYPOGLYCEMIA INDUCED IN MICE BY INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR

Endotoxins or lipopolysaccharides (LPS), when injected into mice, increase serotonin (5-hydroxytryptamine; 5HT) in the liver and produce hypoglycaemia. In the present study, it was found that the cytokines produced by macrophages in response to LPS, interleukin-1 (IL-1, 0.1 mu-g/kg or more) and tumour necrosis factor (TNF-alpha, 100 mu-g/kg or more), can also induce an increase in liver serotonin and produce hypoglycaemia. The two responses correspond well with each other in terms of time course and dose dependency. These results suggest that the two responses induced by LPS may be mediated by IL-1 and/or TNF-alpha and that the phenomenon of accumulation of 5HT in the liver may be relevant to hypoglycaemia. The hypoglycaemic response to IL-1 was moderate at a wide dose range but was induced by smaller amounts than with insulin.