title: Production of interleukin-27 by human neutrophils regulates their function during bacterial infection.
abstract: Septicemia is the most severe form of melioidosis caused by the Gram-negative bacterium, Burkholderia pseudomallei. Here, we show that levels of IL-27p28 transcript and protein were both significantly elevated in patients with sepsis, particularly melioidosis and in patients with unfavorable disease outcome. Moreover, human monocytes/macrophages and neutrophils were the major source of IL-27 during infection. The addition of exogenous IL-27 in vitro resulted in significantly increased bacterial survival, reduced B. pseudomallei-induced oxidative burst, and enhanced IL-1β and TNF-α production by purified neutrophils from healthy subjects. Finally, blockade of endogenous IL-27 in neutrophils using soluble IL-27 receptor antagonist prior to infection led to significantly reduced survival of bacteria and decreased IL-1β, but not TNF-α production. These results indicate a potential role for IL-27 in the suppression of anti-bacterial defense mechanisms that might contribute to disease severity in sepsis. The targeting of this cytokine may be beneficial in the management of human sepsis.
authors.affiliation: The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Darawan
authors.initials: D
authors.lastname: Rinchai
authors.forename: Prasong
authors.initials: P
authors.lastname: Khaenam
authors.forename: Chidchamai
authors.initials: C
authors.lastname: Kewcharoenwong
authors.forename: Surachat
authors.initials: S
authors.lastname: Buddhisa
authors.forename: Rungnapa
authors.initials: R
authors.lastname: Pankla
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bancroft
authors.forename: Ganjana
authors.initials: G
authors.lastname: Lertmemongkolchai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016957:Burkholderia pseudomallei / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008554:Melioidosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology*; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D007378:Interleukins; C464565:MYDGF protein, human; D014409:Tumor Necrosis Factor-alpha