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Role of Central Interleukin-1β in Gastrointestinal Motor Disturbances Induced by Lipopolysaccharide in Sheep

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Abstract

Cytokines are involved in the symptoms of theacute phase response induced by infectious diseases inhumans as well as in animals, and interleukin-1β(IL-1 ) has a pivotal role in these changes. The role of central IL-1β in the gastrointestinalhypomotility and fever evoked by intravenousadministration of lipopolysaccharide (LPS) and themechanisms involved, were investigated in sheep as anexperimental model. LPS (0.1 μg/kg, intravenously)induced gastrointestinal hypomotility and fever thatwere significantly reduced by priorintracerebroventricular administration of IL-1βreceptor antagonist protein (IL-1ra, 2 μg/kg). The effects of LPS were mimickedby intracerebroventricular IL-1β (50 ng/kg),whereas IL-1β injected intravenously at the samedose only caused a slight and transient fever withoutmodifying the gastrointestinal motility. Priorintracerebroventricular administration of thecyclooxygenase inhibitor indomethacin (100 μg/kg) butnot the corticotropin-releasing factor (CRF) receptorantagonist α-helical CRF9-41 (5 μg/kg) blocked alleffects evoked by both LPS and IL-1β. These resultssuggest that in sheep, LPS induces digestive motordisturbances through a central release of IL-1β andprostaglandins.

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Plaza, M.A., Fioramonti, J. & Bueno, L. Role of Central Interleukin-1β in Gastrointestinal Motor Disturbances Induced by Lipopolysaccharide in Sheep. Dig Dis Sci 42, 242–250 (1997). https://doi.org/10.1023/A:1018837112572

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