Roles of IL-1 and TNF in the decreased ileal muscle contractility induced by lipopolysaccharide.
Gastrointestinal stasis during sepsis may be associated with gastrointestinal smooth muscle dysfunction. Endotoxin [lipopolysaccharide (LPS)] impairs smooth muscle contraction, in part through inducible nitric oxide synthase (NOS II) and enhanced nitric oxide production. We studied the roles of tumor necrosis factor-alpha (TNF) and interleukin-1 (IL-1) in this process by using TNF binding protein (TNFbp) and IL-1 receptor antagonist (IL-1ra). Rats were treated with TNFbp and IL-1ra, or their vehicles, 1 h before receiving LPS or saline. At 5 h after LPS, contractility was measured in strips of ileal longitudinal smooth muscle, and NOS II activity was measured in full-thickness segments of ileum. LPS decreased maximum stress (mean +/- SE) from 508 +/- 55 (control) to 355 +/- 33 g/cm2 (P < 0.05). Pretreatment with TNFbp plus IL-1ra prevented the LPS-induced decrease. Separate studies of TNFbp alone or IL-1ra alone indicated that, at the doses and timing used, TNFbp was more effective. LPS also increased NOS II activity by >10-fold (P < 0.01) over control. This increase was prevented by TNFbp plus IL-1ra (P = not significant vs. control). We conclude that the LPS-induced increase in NOS II activity and the decrease in ileal muscle contractility are mediated by TNF and IL-1.
Lodato
R F
RF
Department of Internal Medicine, Trauma Research Center, University of Texas Health Science Center, Houston, Texas 77030, USA. rlodato@heart.med.uth.tmc.edu
Khan
A R
AR
Zembowicz
M J
MJ
Weisbrodt
N W
NW
Pressley
T A
TA
Li
Y F
YF
Lodato
J A
JA
Zembowicz
A
A
Moody
F G
FG
D000818:Animals; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D007082:Ileum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat