Details

Autor(en) / Beteiligte

• PUMMEL, Christoph
• BARTH, Stephan W
• VOSS, Thilo
• KORTE, Stefan
• GERSTBERGER, Rüdiger
• HÜBSCHLE, Thomas
• ROTH, Joachim

Titel

Localized vs. systemic inflammation in guinea pigs : a role for prostaglandins at distinct points of the fever induction pathways?

Ist Teil von

• American journal of physiology. Regulatory, integrative and comparative physiology, 2005-08, Vol.58 (2), p.R340-R347

Ort / Verlag

Bethesda, MD: American Physiological Society

Erscheinungsjahr

2005

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• In guinea pigs, dose-dependent febrile responses were induced by injection of a high (100 micro g/kg) or a low (10 micro g/kg) dose of bacterial lipopolysaccharide (LPS) into artificial subcutaneously implanted Teflon chambers. Both LPS doses further induced a pronounced formation of prostaglandin E2 (PGE2) at the site of localized subcutaneous inflammation. Administration of diclofenac, a nonselective cyclooxygenase (COX) inhibitor, at different doses (5, 50, 500, or 5,000 micro g/kg) attenuated or abrogated LPS-induced fever and inhibited LPS-induced local PGE2 formation (5 or 500 micro g/kg diclofenac). Even the lowest dose of diclofenac (5 micro g/kg) attenuated fever in response to 10 micro g/kg LPS, but only when administered directly into the subcutaneous chamber, and not into the site contralateral to the chamber. This observation indicated that a localized formation of PGE2 at the site of inflammation mediated a portion of the febrile response, which was induced by injection of 10 µg/kg LPS into the subcutaneous chamber. Further support for this hypothesis derived from the observation that we failed to detect elevated amounts of COX-2 mRNA in the brain of guinea pigs injected subcutaneously with 10 micro g/kg LPS, whereas subcutaneous injections of 100 micro g/kg LPS, as well as systemic injections of LPS (intra-arterial or intraperitoneal routes), readily caused expression of the COX-2 gene in the guinea pig brain, as demonstrated by in situ hybridization. Therefore, fever in response to subcutaneous injection of 10 micro g/kg LPS may, in part, have been evoked by a neural, rather than a humoral, pathway from the local site of inflammation to the brain. [PUBLICATION ABSTRACT]