Central tumour necrosis factor‐α mediates the early gastrointestinal motor disturbances induced by lipopolysaccharide in sheep

• Published in: Neurogastroenterology and motility Vol. 15; no. 3; pp. 307 - 316
• Main Authors: Guerrero‐Lindner, E., Castro, M., MuÑoz, J. M., Arruebo, M. P., Murillo, M.D., Buéno, L., Plaza, M.A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2003
• Subjects: Animals; body temperature; Body Temperature - drug effects; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; cytokines; Female; fever; Fever - chemically induced; gastrointestinal motility; Gastrointestinal Motility - drug effects; Humans; Immunoglobulin Fc Fragments; Indomethacin - administration & dosage; Indomethacin - pharmacology; Injections, Intravenous; Injections, Intraventricular; Lipopolysaccharides - pharmacology; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Myoelectric Complex, Migrating - drug effects; prostaglandins; Receptors, Tumor Necrosis Factor - administration & dosage; Recombinant Proteins; sheep; Sheep, Domestic; Tumor Necrosis Factor-alpha - administration & dosage; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1046/j.1365-2982.2003.00402.x

Cytokines are involved in fever and other symptoms of the acute phase response induced by endotoxins. The aim of this work was to study the involvement of central tumour necrosis factor‐α (TNF‐α) in the changes induced by lipopolysaccharide (LPS) on gastrointestinal (GI) motility in sheep. Body temperature and myoelectric activity of the antrum, duodenum and jejunum was recorded continuously. Intravenous (i.v.) administration of LPS (0.1 μg kg−1)‐induced hyperthermia, decreased gastrointestinal myoelectric activity and increased the frequency of the migrating motor complex (MMC). These effects started 40–50 min after LPS and lasted for 6–7 h. TNF‐α (50 and 100 ng kg−1) mimicked these effects when injected intracerebroventricularly (i.c.v.) but not i.v. Pretreatment with soluble recombinant TNF receptor (TNFR:Fc, 10 μg kg−1, i.c.v.) abolished the TNF‐induced actions and reduced those evoked by LPS. Furthermore, the effects induced by either LPS or TNF were suppressed by prior i.c.v. injection of indomethacin (100 μg kg−1). In contrast, the i.v. injections of TNFR:Fc or indomethacin were ineffective. Our data suggest that LPS disturbs GI motility in sheep through a central pathway that involves TNF‐α and prostaglandins sequentially.