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We have investigated the contribution of inflammatory responses induced by the venom metalloproteinase jararhagin (isolated from <jats:italic>Bothrops jararaca<\/jats:italic> venom) in the development of these lesions. Local venom effects (edema, hemorrhage and necrosis) were inducedexperimentally in knockout mice deficient in the TNF receptors TNFR1 or TNFR2, IL\u20101\u03b2R, IL\u20106 and iNOS. Jararhagin\u2010induced dermal necrosis was abolished in mice deficient in the TNF receptors TNFR1 and TNFR2, and the same activity was significantly reduced in IL\u20106<jats:sup>\u2013\/\u2013<\/jats:sup> mice. There was no significant difference in edema and hemorrhage activities following jararhagin insult between knockout and WT strains, indicating that these local venom metalloproteinase\u2010induced effects are independent of these pro\u2010inflammatory mediators. The contribution of both TNF receptors and IL\u20106 in local tissue necrosis raises important therapeutic issues regarding the treatment of local envenoming.<\/jats:p>","DOI":"10.1002\/eji.200324475","type":"journal-article","created":{"date-parts":[[2003,11,20]],"date-time":"2003-11-20T18:07:53Z","timestamp":1069351673000},"page":"3458-3463","source":"Crossref","is-referenced-by-count":85,"title":["Inflammatory pathogenesis of snake venom metalloproteinase\u2010induced skin necrosis"],"prefix":"10.1002","volume":"33","author":[{"given":"Gavin\u2004David","family":"Laing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia\u2004Bianca","family":"Clissa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert\u2004David\u2004Geoffrey","family":"Theakston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u2004Maria","family":"Moura\u2010da\u2010Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u2004John","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,11,19]]},"reference":[{"key":"e_1_2_7_1_2","first-page":"345","article-title":"Symptomatology, pathology and treatment of snake bites in South America. 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