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

Abstract

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-alpha (TNF-alpha) 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 micro g 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-alpha (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 micro g 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 micro g 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-alpha and prostaglandins sequentially.

Oral Erythromycin Accelerates Impaired Gastrointestinal Motility After Endoscopic Mucosal Resection

“…Mucosal inflammation activates leukocytes in the gastric wall, which release immunoregulatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α [28][29][30][31], while nitric oxide (NO) production also increases due to induction of NO synthase [32]. Some of these cytokines are known to interfere with gastrointestinal motility [33][34][35][36], while NO inhibits gastric emptying and antral motility [37]. Therefore, cytokines and NO or other inflammatory mediators released from the injured gastric wall may disturb gastrointestinal motility.…”

The Gut is not only the Target but a Source of Inflammatory Mediators Inhibiting Gastrointestinal Motility During Sepsis

“…The activation of TLR4 leads to an activation of the nuclear factor-κB (NF-κB), stimulating the synthesis of pro-inflammatory cytokines [18]. TNFα is known to inhibit smooth muscle contractions [19] and is capable of inhibiting gastrointestinal motility when injected centrally [20]. It was shown that TNFα binding protein protects animals from LPS induced intestinal dysmotility [21].…”

“…The mechanism of TNFα on gastrointestinal motility is not completely understood. As mentioned above, circulating TNFα is capable of inhibiting both smooth muscle activity in the gut and central neural pathways regulating gastrointestinal motility by passing the blood brain barrier [20,24,25]. However, it is also possible that TNFα itself plays a minor role in inhibiting gastrointestinal motility, as it instead stimulates other cells releasing mediators which inhibit gastrointestinal motility.…”

Disturbances of Gastric Electrical Control Activity after Laparotomic Cholecystectomy Are Related to Interleukin-6 Concentrations

“…Experimental findings suggest the role of various cytokines and other mediators in gastrointestinal motility disturbances [14, 15]. Resident intestinal muscularis macrophages are rapidly activated after surgical injury and may be involved in inflammatory responses resulting in postoperative ileus [16].…”