title: Heme oxygenase-1 induction by cobalt protoporphyrin enhances fever and inhibits pyrogenic tolerance to lipopolysaccharide.
abstract: Heme oxygenase-1 (HO-1) is an enzyme that catalyzes degradation of the heme and regulates its availability for newly synthetized hemeproteins such as cyclooxygenases, NO synthases and cytochrome P450. Moreover, HO-1 activity modulates synthesis of cytokines and prostaglandins. All of these factors are well-defined components of fever and pyrogenic tolerance mechanisms. We examine the effect of HO-1 induction and activation using cobalt protoporphyrin (CoPP) on changes in body temperature (Tb), plasma levels of interleukin-6 (IL-6), prostaglandin E₂ (PGE₂) and HO-1 protein in the course of these processes. Intraperitoneally (i.p.) pre-treatment of rats with CoPP (5 mg kg(-1)) significantly accelerated and enhanced the early stage of lipopolysaccharide (LPS)-induced fever and shortened a post-fever recovery to normal temperature. Pre-treatment with CoPP significantly potentiated the increase in plasma IL-6, PGE₂ and HO-1 levels measured 4h after the LPS administration. Furthermore, induction of HO-1 attenuated the development of pyrogenic tolerance to repeated injections of LPS. Based on these data we conclude that heme oxygenase-1 may act as a physiological regulator of the febrile response intensity to bacterial infections.
authors.affiliation: Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Wilenska 4 Street, Torun 87-100, Poland; Department of Immunology, Faculty of Biology and Environment Protection, Nicolaus Copernicus University, 1 Lwowska Street, Torun 87-100, Poland. Electronic address: piotrowski_jak@umk.pl.
authors.forename: Jakub
authors.initials: J
authors.lastname: Piotrowski
authors.affiliation: Department of Immunology, Faculty of Biology and Environment Protection, Nicolaus Copernicus University, 1 Lwowska Street, Torun 87-100, Poland. Electronic address: tomaszj@umk.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jedrzejewski
authors.affiliation: Department of Immunology, Faculty of Biology and Environment Protection, Nicolaus Copernicus University, 1 Lwowska Street, Torun 87-100, Poland. Electronic address: wkozak@umk.pl.
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Kozak
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000097:blood; D005334:Fever / Q000209:etiology / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D011524:Protoporphyrins / Q000494:pharmacology*; D011749:Pyrogens / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D011524:Protoporphyrins; D011749:Pyrogens; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1; D015232:Dinoprostone
keywords: Fever; Heme oxygenase; Interleukin-6; Lipopolysaccharide; Prostaglandin E(2); Pyrogenic tolerance