title: Peripheral injection of SB203580 inhibits the inflammatory-dependent synthesis of proinflammatory cytokines in the hypothalamus.
abstract: The study was designed to determine the effects of peripheral injection of SB203580 on the synthesis of interleukin- (IL-) 1β, IL-6, and tumor necrosis factor (TNF) α in the hypothalamus of ewes during prolonged inflammation. Inflammation was induced by the administration of lipopolysaccharide (LPS) (400 ng/kg) over 7 days. SB203580 is a selective ATP-competitive inhibitor of the p38 mitogen-activated protein kinase (MAPK), which is involved in the regulation of proinflammatory cytokines IL-1β, IL-6 and TNFα synthesis. Intravenous injection of SB203580 successfully inhibited (P < 0.01) synthesis of IL-1β and reduced (P < 0.01) the production of IL-6 in the hypothalamus. The p38 MAPK inhibitor decreased (P < 0.01) gene expression of TNFα but its effect was not observed at the level of TNFα protein synthesis. SB203580 also reduced (P < 0.01) LPS-stimulated IL-1 receptor type 1 gene expression. The conclusion that inhibition of p38 MAPK blocks LPS-induced proinflammatory cytokine synthesis seems to initiate new perspectives in the treatment of chronic inflammatory diseases also within the central nervous system. However, potential proinflammatory effects of SB203580 treatment suggest that all therapies using p38 MAPK inhibitors should be introduced very carefully with analysis of all expected and unexpected consequences of treatment.
authors.affiliation: Polish Academy of Sciences, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland.
authors.forename: Andrzej P
authors.initials: AP
authors.lastname: Herman
authors.affiliation: Polish Academy of Sciences, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Krawczyńska
authors.affiliation: Polish Academy of Sciences, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland.
authors.forename: Joanna
authors.identifier: 0000-0002-0821-0059
authors.initials: J
authors.lastname: Bochenek
authors.affiliation: Polish Academy of Sciences, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Antushevich
authors.affiliation: The Academy of Cosmetics and Health Care, 13 Podwale Street, 00-252 Warsaw, Poland.
authors.forename: Anna
authors.identifier: 0000-0002-2722-6195
authors.initials: A
authors.lastname: Herman
authors.affiliation: Polish Academy of Sciences, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland.
authors.forename: Dorota
authors.identifier: 0000-0002-2619-4638
authors.initials: D
authors.lastname: Tomaszewska-Zaremba
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007267:Injections; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D007093:Imidazoles; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C093642:SB 203580