title: Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection.
abstract: Type 2 diabetes mellitus is a major risk factor for melioidosis, which is caused by Burkholderia pseudomallei. Our previous study has shown that polymorphonuclear neutrophils (PMNs) from diabetic subjects exhibited decreased functions in response to B. pseudomallei. Here we investigated the mechanisms regulating cytokine secretion of PMNs from diabetic patients which might contribute to patient susceptibility to bacterial infections. Purified PMNs from diabetic patients who had been treated with glibenclamide (an ATP-sensitive potassium channel blocker for anti-diabetes therapy), showed reduction of interleukin (IL)-1β and IL-8 secretion when exposed to B. pseudomallei. Additionally, reduction of these pro-inflammatory cytokines occurred when PMNs from diabetic patients were treated in vitro with glibenclamide. These findings suggest that glibenclamide might be responsible for the increased susceptibility of diabetic patients, with poor glycemic control, to bacterial infections as a result of its effect on reducing IL-1β production by PMNs.
authors.affiliation: The Centre for Research & Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.
authors.forename: Chidchamai
authors.initials: C
authors.lastname: Kewcharoenwong
authors.forename: Darawan
authors.initials: D
authors.lastname: Rinchai
authors.forename: Kusumawadee
authors.initials: K
authors.lastname: Utispan
authors.forename: Duangchan
authors.initials: D
authors.lastname: Suwannasaen
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bancroft
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.forename: Ganjana
authors.initials: G
authors.lastname: Lertmemongkolchai
mesh_terms: D016957:Burkholderia pseudomallei / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000276:immunology*; D004198:Disease Susceptibility / Q000139:chemically induced / Q000276:immunology; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D008554:Melioidosis / Q000276:immunology / Q000382:microbiology; D008687:Metformin / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology; D013785:Thailand
chemical_list: C508606:CXCL8 protein, human; D007004:Hypoglycemic Agents; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; D008687:Metformin; D005905:Glyburide