C. Hierholzer et al., Nuclear factor-kappa B (NF-kappa B) regulates nitric oxide (NO) induced intestinal inflammation and stasis following hemorrhagic shock, LANG ARCH S, 1999, pp. 577-581
Background: In hemorrhagic shock (HS) increased cytokine production contrib
utes to gut inflammation and impairment of smooth muscle function through t
he recruitment of PMN. NO-mediated activation of NF-kappa B can result in t
he induction of cytokines that contain NF-kappa B bindings sites. Experimen
ts were performed to determine the contribution of induced NO to gut inflam
mation and dysmotility in HS.
Materials and Methods: Sprague-Dawley rats were subjected to severe HS (40
mmHg MAP for 2.5 hours) followed by resuscitation and sacrifice at 4 hours.
The selective iNOS inhibitor L-NIL (50 mg/kg body weight) was administered
intravenously during the decompensation phase. We determined IL-6 mRNA lev
els using RT-PCR and activation of NF-kappa B and Stat3 using EMSA gel shif
t. Jejunal damage was assessed using histology, PMN infiltration, and smoot
h muscle contractility.
Results: In this study we demonstrate an attenuated inflammatory response i
n the jejunum of animals subjected to severe HS and treated with L-NIL. L-N
IL-treated animals demonstrated significant reduction in IL-6 mRNA expressi
on (57%), reduction in NF-kappa B (57%) and Stat3 activity (38%), reduction
in PMN infiltration (58%) and attenuated organ damage. Furthermore, muscle
contractility was almost completely restored.
Conclusions: We propose that early upregulation of iNOS contributes signifi
cantly to the activation of NF-kappa B resulting in proinflammatory cytokin
e production in the gut wall ultimately leading to PMN recruitment and impa
ired motility. Thus, reducing induced NO bioavailability following severe H
S may improve gut function through downmodulation of NF-kappa B.