{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T10:54:29Z","timestamp":1759056869780},"reference-count":18,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":3839,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1998,8]]},"abstract":"<jats:p>The cytokine tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) is involved (mostly through the activation of inducible nitric oxide synthase) in the pathogenesis of circulatory shock. On the other hand, melanocortin peptides are potent and effective in reversing haemorrhagic shock, both in animals (rat, dog) and in humans. This prompted us to study the influence of the melanocortin peptide ACTH\u2010(1\u201324) on the blood levels of TNF\u2010\u03b1 in haemorrhage\u2010shocked rats and on the <jats:italic>in vitro<\/jats:italic> production of TNF\u2010\u03b1 by lipopolysaccharide (LPS)\u2010activated macrophages. Plasma levels of TNF\u2010\u03b1 were undetectable before starting bleeding and greatly increased 20\u2003min after bleeding termination in saline\u2010treated rats. In rats treated with ACTH\u2010(1\u201324) the almost complete restoration of cardiovascular function was associated with markedly reduced levels of TNF\u2010\u03b1 20\u2003min after bleeding termination. On the other hand, ACTH\u2010(1\u201324) did not influence TNF\u2010\u03b1 plasma levels in sham\u2010operated, unbled rats. <jats:italic>In vitro<\/jats:italic>, ACTH\u2010(1\u201324) (25\u2013100\u2003n<jats:sc>M<\/jats:sc>) dose\u2010dependently reduced the LPS\u2010stimulated production of TNF\u2010\u03b1 by peritoneal macrophages harvested from untreated, unbled rats. These results indicate that inhibition of TNF\u2010\u03b1 overproduction may be an important component of the mechanism of action of melanocortins in reversing haemorrhagic shock.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>124<\/jats:bold>, 1587\u20131590; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702038\">10.1038\/sj.bjp.0702038<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702038","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:35:54Z","timestamp":1106940954000},"page":"1587-1590","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Tumour necrosis factor\u2010<i>\u03b1<\/i> as a target of melanocortins in haemorrhagic shock, in the anaesthetized rat"],"prefix":"10.1111","volume":"124","author":[{"given":"Domenica","family":"Altavilla","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria\u2010Michela","family":"Cainazzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Squadrito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Guarini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfio","family":"Bertolini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Bazzani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"584","article-title":"HP\u2010228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro","volume":"275","author":"Abou\u2010Mohamed G.","year":"1995","journal-title":"J. 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