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Here, we examined whether the antipyretic effect of paracetamol was due to TRPA1 activation or cyclooxygenase inhibition. Treatment of wild\u2010type and TRPA1 knockout mice rendered febrile by immune challenge with LPS with a dose of paracetamol that did not produce hypothermia (150 mg\/kg) but is known to be analgetic, abolished fever in both genotypes. Paracetamol completely suppressed the LPS\u2010induced elevation of prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    in the brain and also reduced the levels of several other prostanoids. The hypothermia induced by paracetamol was abolished in mice treated with the electrophile\u2010scavenger N\u2010acetyl cysteine. We conclude that paracetamol's antipyretic effect in mice is dependent on inhibition of cyclooxygenase activity, including the formation of pyrogenic prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    , whereas paracetamol\u2010induced hypothermia likely is mediated by the activation of TRPA1 by electrophilic metabolites of paracetamol, similar to its analgesic effect in some experimental paradigms.\u2014Mirrasekhian, E., Nilsson, J. L. \u00c5., Shionoya, K., Blomgren, A., Zygmunt, P. M., Engblom, D., H\u00f6gest\u00e4tt, E. D., Blomqvist, A. The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1\u2010mediated hypothermia and is associated with prostaglandin inhibition in the brain.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    32, 5751\u20135759 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201800272r","type":"journal-article","created":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T15:34:58Z","timestamp":1525793698000},"page":"5751-5759","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1\u2010mediated hypothermia and is associated with prostaglandin inhibition in the 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