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Induction of endogenous tumor necrosis factor-alpha: suppression of centrally stimulated gastric motility.

Abstract

Gastric stasis is frequently seen in conjunction with critical infectious illness, chronic inflammatory disorders, radiation sickness, and carcinogenesis. These conditions are associated with elevated circulating levels of the cytokine tumor necrosis factor-alpha (TNF-alpha). The present studies examined the relationship between endogenously produced TNF-alpha and the central neural mechanisms that augment gastric motility. Systemic lipopolysaccharide (LPS) was employed to induce TNF-alpha production in thiobutabarbital-anesthetized rats. Sixty minutes after intravenous LPS injection, gastric motility could not be stimulated by a potent centrally acting gastrokinetic stimulant, thyrotropin-releasing hormone (TRH). This failure to elicit gastric motility via central mechanisms coincided with high circulating levels of TNF-alpha. However, intravenous injections of bethanecol, a peripherally acting cholinergic agonist with direct gastrokinetic effects, were still able to elicit normal increases in gastric motility in the presence of TNF-alpha and LPS. Therefore, the inability to stimulate gastric motility via central TRH could not be attributed to the direct inhibitory effects of either LPS or TNF-alpha on the stomach. If the production of endogenous TNF-alpha was suppressed via the use of urethan as the anesthetic agent, then intravenous injections of LPS were no longer effective in suppressing gastric motility. Thus these effects on gastric motility are not directly attributable to LPS nor are they due to direct effects on the gastric smooth muscle. Our previous study demonstrated that microinjection of femtomole quantities of TNF-alpha in the brain stem dorsal vagal complex (DVC) can modulate gastric motility. This central TNF-alpha effect on gastric motility was dose dependent and required an intact vagal efferent pathway. The results from these two studies suggest that systemically produced TNF-alpha may gain access to the DVC to modulate gastric function.

Authors+Show Affiliations

,

Department of Physiology, College of Medicine, Ohio State University, Columbus, Ohio 43210, USA.

,

Source

The American journal of physiology 276:1 1999 01 pg R59-68

MeSH

Animals
Bethanechol
Cerebral Ventricles
Gastrointestinal Motility
Injections, Intravenous
Male
Muscarinic Agonists
Rats
Rats, Long-Evans
Thyrotropin-Releasing Hormone
Tumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9887178

Citation

Hermann, G E., et al. "Induction of Endogenous Tumor Necrosis Factor-alpha: Suppression of Centrally Stimulated Gastric Motility." The American Journal of Physiology, vol. 276, no. 1, 1999, pp. R59-68.
Hermann GE, Tovar CA, Rogers RC. Induction of endogenous tumor necrosis factor-alpha: suppression of centrally stimulated gastric motility. Am J Physiol. 1999;276(1):R59-68.
Hermann, G. E., Tovar, C. A., & Rogers, R. C. (1999). Induction of endogenous tumor necrosis factor-alpha: suppression of centrally stimulated gastric motility. The American Journal of Physiology, 276(1), pp. R59-68. doi:10.1152/ajpregu.1999.276.1.R59.
Hermann GE, Tovar CA, Rogers RC. Induction of Endogenous Tumor Necrosis Factor-alpha: Suppression of Centrally Stimulated Gastric Motility. Am J Physiol. 1999;276(1):R59-68. PubMed PMID: 9887178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of endogenous tumor necrosis factor-alpha: suppression of centrally stimulated gastric motility. AU - Hermann,G E, AU - Tovar,C A, AU - Rogers,R C, PY - 1999/1/14/pubmed PY - 1999/1/14/medline PY - 1999/1/14/entrez SP - R59 EP - 68 JF - The American journal of physiology JO - Am. J. Physiol. VL - 276 IS - 1 N2 - Gastric stasis is frequently seen in conjunction with critical infectious illness, chronic inflammatory disorders, radiation sickness, and carcinogenesis. These conditions are associated with elevated circulating levels of the cytokine tumor necrosis factor-alpha (TNF-alpha). The present studies examined the relationship between endogenously produced TNF-alpha and the central neural mechanisms that augment gastric motility. Systemic lipopolysaccharide (LPS) was employed to induce TNF-alpha production in thiobutabarbital-anesthetized rats. Sixty minutes after intravenous LPS injection, gastric motility could not be stimulated by a potent centrally acting gastrokinetic stimulant, thyrotropin-releasing hormone (TRH). This failure to elicit gastric motility via central mechanisms coincided with high circulating levels of TNF-alpha. However, intravenous injections of bethanecol, a peripherally acting cholinergic agonist with direct gastrokinetic effects, were still able to elicit normal increases in gastric motility in the presence of TNF-alpha and LPS. Therefore, the inability to stimulate gastric motility via central TRH could not be attributed to the direct inhibitory effects of either LPS or TNF-alpha on the stomach. If the production of endogenous TNF-alpha was suppressed via the use of urethan as the anesthetic agent, then intravenous injections of LPS were no longer effective in suppressing gastric motility. Thus these effects on gastric motility are not directly attributable to LPS nor are they due to direct effects on the gastric smooth muscle. Our previous study demonstrated that microinjection of femtomole quantities of TNF-alpha in the brain stem dorsal vagal complex (DVC) can modulate gastric motility. This central TNF-alpha effect on gastric motility was dose dependent and required an intact vagal efferent pathway. The results from these two studies suggest that systemically produced TNF-alpha may gain access to the DVC to modulate gastric function. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/9887178/full_citation DB - PRIME DP - Unbound Medicine ER -