title: N-Acetyl-l-cysteine exacerbates generation of IL-10 in cells stimulated with endotoxin in vitro and produces antipyresis via IL-10 dependent pathway in vivo.
abstract: N-Acetyl-l-cysteine (NAC) is a well-known medication, primarily used as a mucolytic agent in pulmonary disease. Recently, we have found that NAC possesses antipyretic properties. The aim of the present study was to investigate the mechanism by which NAC attenuates fever. The concentration of interleukin (IL)-10 and prostaglandin (PG) E2 were measured using ELISA kit in the supernatants aspirated after stimulation of peripheral blood mononuclear cells (PBMCs) with lipopolysaccharide (LPS, 1μg/mL) and NAC (10mM). The body temperature of the Wistar rats was measured using biotelemetry system. To inhibit endotoxic fever, NAC (200mg/kg; i.p.) was injected into the rats one hour prior to the LPS administration (50μg/kg; i.p.). The pre-treatment of LPS-stimulated PBMCs with NAC resulted in a significant decrease in PGE2 concentration in comparison to the cells treated with LPS alone (PGE2 level was 386.1±61.9pg/mL vs. 2078.9±157.9pg/mL, respectively, p<0.001). Furthermore, in these cells we observed a significant increase in IL-10 level (142.1±2.62pg/mL in NAC+LPS stimulated cells vs. 54.4±0.6pg/mL in LPS stimulated cells, p<0.001). The injection of anti-IL-10 antibody into the rats abolished antipyretic properties of NAC. Body temperature in animals treated with anti-IL-10+NAC/LPS was 38.28±0.12°C vs. 37.73±0.06°C in IgG+NAC/LPS rats (p<0.001) and 38.31±0.20°C in NaCl/LPS-treated animals (n.s.). Based on these data, we conclude that NAC acts as an antipyretic via IL-10 stimulation. This finding provides a new insight into the immunopharmacology of NAC, and we believe that in a future it will contribute to the new and/or more accurate application of NAC in medicine.
authors.affiliation: Department of Immunology, Nicolaus Copernicus University, Ul. Lwowska 1, 87-100, Torun, Poland. Electronic address: wrotek@umk.pl.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Wrotek
authors.affiliation: Department of Immunology, Nicolaus Copernicus University, Ul. Lwowska 1, 87-100, Torun, Poland. Electronic address: tomaszj@umk.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jędrzejewski
authors.affiliation: Department of Immunology, Nicolaus Copernicus University, Ul. Lwowska 1, 87-100, Torun, Poland; Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Wilenska 4, 87-100, Torun, Poland. Electronic address: piotrowski_jak@umk.pl.
authors.forename: Jakub
authors.initials: J
authors.lastname: Piotrowski
authors.affiliation: Department of Immunology, Nicolaus Copernicus University, Ul. Lwowska 1, 87-100, Torun, Poland. Electronic address: wkozak@umk.pl.
authors.forename: Wiesław
authors.initials: W
authors.lastname: Kozak
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D058633:Antipyretics / Q000494:pharmacology*; D001831:Body Temperature; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005334:Fever / Q000188:drug therapy* / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019138:Antibodies, Blocking; D058633:Antipyretics; D008070:Lipopolysaccharides; D016753:Interleukin-10; D015232:Dinoprostone; D000111:Acetylcysteine
keywords: Antipyresis; Endotoxin; Fever; IL-10; N-Acetyl-l-cysteine