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The effect of lipopolysaccharide, interleukin‐1 and tumour necrosis factor on the hepatic accumulation of 5‐hydroxytryptamine and platelets in the mouse
Author(s) -
Endo Yasuo,
Nakamura Masanori
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb09028.x
Subject(s) - endocrinology , medicine , lipopolysaccharide , reserpine , platelet , histamine , tumor necrosis factor alpha , spleen , serotonin , chemistry , mast cell , stimulation , biology , immunology , receptor
1 Injection of lipopolysaccharide (LPS; 0.5–500 μg 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 μg 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, α and β (10 μg kg −1 ) and tumour necrosis factor α (TNFα) (1 mg kg −1 ) significantly enhanced the accumulation of 5‐HT within the liver. Administration of TNFα (10 μg kg −1 ) potentiated the increase in hepatic 5‐HT content seen with IL‐1β (10 μg 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.