HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 98/4/1322    most recent 01243.2004v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Dias, M. B. Articles by Branco, L. G. S. Search for Related Content PubMed PubMed Citation Articles by Dias, M. B. Articles by Branco, L. G. S.

Role of nitric oxide in tolerance to lipopolysaccharide in mice

¹Department of Physiology, Medical School of Ribeirão Preto, University of São Paulo, ²Department of General and Specialized Nursing, Nursing School of Ribeirão Preto, and ³Department of Morphology, Estomatology and Physiology, Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

Submitted 4 November 2004 ; accepted in final form 30 November 2004

The injection of repeated doses of lipopolysaccharide (LPS) results in attenuation of the febrile response, which is called endotoxin tolerance. We tested the hypothesis that nitric oxide (NO) arising from inducible NO synthase (iNOS) plays a role in endotoxin tolerance, using not only pharmacological trials but also genetically engineered mice. Body core temperature was measured by biotelemetry in mice treated with N^G-monomethyl-L-arginine (L -NMMA, 40 mg/kg; a nonselective NO synthase inhibitor) or aminoguanidine (AG, 10 mg/kg; a selective iNOS inhibitor) and in mice deficient in the iNOS gene (iNOS KO) mice. Tolerance to LPS was induced by means of three consecutive LPS (100 µg/kg) intraperitoneal injections at 24-h intervals. In wild-type mice, we observed a significant reduction of the febrile response to repeated administration of LPS. Injection of L-NMMA and AG markedly enhanced the febrile response to LPS in tolerant animals. Conversely, iNOS-KO mice repeatedly injected with LPS did not become tolerant to the pyrogenic effect of LPS. These data are consistent with the notion that NO modulates LPS tolerance in mice and that iNOS isoform is involved in NO synthesis during LPS tolerance.

body temperature; thermoregulation; fever; nitric oxide synthase

This article has been cited by other articles:

				A. Draisma, M. Dorresteijn, P. Pickkers, and H. van der Hoeven The effect of systemic iNOS inhibition during human endotoxemia on the development of tolerance to different TLR-stimuli Innate Immunity, June 1, 2008; 14(3): 153 - 159. [Abstract] [PDF]