THE EFFECT OF LIPOPOLYSACCHARIDE, INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR ON THE HEPATIC ACCUMULATION OF 5-HYDROXYTRYPTAMINE AND PLATELETS IN THE MOUSE

1 Injection of lipopolysaccharide (LPS; 0.5-500-mu-g kg-1) into mice induced a dose-dependent, slowly developing increase in hepatic content of 5-hydroxytryptamine (5-HT). This sustained increase could not be attributed to an LPS-induced alteration of the pharmacokinetic handling of 5-HT by stimulation of its uptake or inhibition of its degradation. 2 Regional differences were apparent in the tissue content of histamine and 5-HT between mast cell-deficient (W/W(v)) and normal (+/+) mice. LPS administration (0.5 mg kg-1) gave comparable increases in the hepatic level of 5-HT in mast cell-deficient and normal mice. 3 Reserpine pretreatment (1 mg kg-1) selectively reduced 5-HT levels in the blood, spleen, liver, brain and lung of normal mice. Prior treatment with this agent also abolished the LPS (0.5 mg kg-1)-induced hepatic accumulation of 5-HT. 4 Accumulation of 5-HT in the liver by LPS (0.1 mg kg-1) was temporally associated with both a fall in the levels of circulating platelets, and a reduction in the concentration of 5-HT in the blood. The LPS dose-dependent (0.5-500-mu-g kg-1) increase in hepatic 5-HT content was associated with a similar dose-dependent reduction in the circulating levels of 5-HT. 5 Interleukin-1, alpha and beta (10-mu-g kg-1) and tumour necrosis factor alpha (TNF-alpha) (1 mg kg-1) significantly enhanced the accumulation of 5-HT within the liver. Administration of TNF-alpha (10-mu-g kg-1) potentiated the increase in hepatic 5-HT content seen with IL-1-beta (10-mu-g kg-1). 6 Electron microscopy revealed numerous platelets in the sinusoidal and perisinusoidal Disse spaces within the liver, in animals pretreated with LPS (0.1 mg kg-1). The platelets retained their intact structure and showed no evidence of degranulation. 7 These data suggest that the LPS and cytokine-induced mobilization of 5-HT in the liver is associated with the hepatic translocation of platelets. This migration appears to be independent of platelet aggregation.