title: Buthionine sulfoximine, a glutathione depletor, attenuates endotoxic fever and reduces IL-1β and IL-6 level in rats.
abstract: The aim of our study was to investigate the effect of buthionine sulfoximine (BSO) - a glutathione depletor - on a course of endotoxic fever and IL-1β and IL-6 production.
  
  
  
  Male Wistar rats were subjected to intraperitoneal injection of lipopolysaccharide (LPS) from E. coli (50μg/kg, ip) to provoke fever. The level of spleen glutathione, plasma interleukin (IL)-1β, IL-6, and deep body temperature (Tb) were measured.
  
  
  
  The LPS administration provoked fever (the average Tb was 38.14±0.05°C in NaCl/LPS-treated rats vs 37.10±0.03°C in control, not-treated rats; p<0.001). We observed that LPS injection induced a decrease in spleen glutathione level (7.67±0.92nM/g vs 13.27±0.47nM/g in not-treated rats; p<0.001). Furthermore, the injection of LPS provoked an elevation of plasma IL-1β and IL-6 concentration (from values below the lowest detectable standard in not-treated animals to 199.99±34.89pg/mL and 7500±542.21pg/mL, respectively; p<0.001). Pretreatment with BSO enhanced glutathione decrease in LPS-treated rats (5.05±0.49nM/g), and significantly affected fever (maximal Tb was 37.81±0.07°C in BSO/LPS-treated rats vs 38.76±0.11°C in NaCl/LPS-treated rats). BSO 4h after LPS injection decreased IL-1β and IL-6 gene expression (about 1.5 fold, and 2 fold, respectively). In a consequence we observed a decrease in plasma IL-6 concentration (4h after LPS injection plasma IL-6 was 4167.17±956.54pg/mL in BSO/LPS-treated rats vs 7500±542.21pg/mL in NaCl/LPS-treated rats; p<0.001), and later IL-1β (7h after LPS injection the IL-1β concentration was not detected).
  
  
  
  Based on these data, we conclude that BSO, in addition to well-known application as an inhibitor of glutathione synthesis, is an antipyretic agent which reduces both IL-1β and IL-6 concentration.
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: Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Wilenska 4, 87-100 Torun, Poland. Electronic address: krydom@umk.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Domagalski
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. Electronic address: ejc.dec@gamil.com.
authors.forename: Eliza
authors.initials: E
authors.lastname: Dec
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: D000818:Animals; D058633:Antipyretics / Q000494:pharmacology*; D005334:Fever / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D053583:Interleukin-1beta / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013454:Sulfoxides / Q000494:pharmacology*
chemical_list: D058633:Antipyretics; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013454:Sulfoxides; C000594507:buthionine sulfoxide; D008715:Methionine
keywords: BSO; Fever; IL-1β; IL-6; Inflammation