title: Interleukin 10 inhibits pro-inflammatory cytokine responses and killing of Burkholderia pseudomallei.
abstract: Melioidosis, caused by Burkholderia pseudomallei, is endemic in northeastern Thailand and Northern Australia. Severe septicemic melioidosis is associated with high levels of pro-inflammatory cytokines and is correlated with poor clinical outcomes. IL-10 is an immunoregulatory cytokine, which in other infections can control the expression of pro-inflammatory cytokines, but its role in melioidosis has not been addressed. Here, whole blood of healthy seropositive individuals (n = 75), living in N. E. Thailand was co-cultured with B. pseudomallei and production of IL-10 and IFN-γ detected and the cellular sources identified. CD3-CD14+monocytes were the main source of IL-10. Neutralization of IL-10 increased IFN-γ, IL-6 and TNF-α production and improved bacteria killing. IFN-γ production and microbicidal activity were impaired in individuals with diabetes mellitus (DM). In contrast, IL-10 production was unimpaired in individuals with DM, resulting in an IL-10 dominant cytokine balance. Neutralization of IL-10 restored the IFN-γ response of individuals with DM to similar levels observed in healthy individuals and improved killing of B. pseudomallei in vitro. These results demonstrate that monocyte derived IL-10 acts to inhibit potentially protective cell mediated immune responses against B. pseudomallei, but may also moderate the pathological effects of excessive cytokine production during sepsis.
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Bianca
authors.initials: B
authors.lastname: Kessler
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Darawan
authors.initials: D
authors.lastname: Rinchai
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chidchamai
authors.initials: C
authors.lastname: Kewcharoenwong
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Arnone
authors.initials: A
authors.lastname: Nithichanon
authors.affiliation: Department of Immunology and Infection, London School of Hygiene &Tropical Medicine, London, United Kingdom.
authors.forename: Rachael
authors.initials: R
authors.lastname: Biggart
authors.affiliation: Department of Asthma, Allergy and Respiratory Science, Guys Hospital, Kings College, London, United Kingdom.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hawrylowicz
authors.affiliation: Department of Immunology and Infection, London School of Hygiene &Tropical Medicine, London, United Kingdom.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bancroft
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ganjana
authors.initials: G
authors.lastname: Lertmemongkolchai
mesh_terms: D000328:Adult; D000368:Aged; D016957:Burkholderia pseudomallei / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D019353:Endemic Diseases; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008554:Melioidosis / Q000276:immunology*; D008875:Middle Aged; D013785:Thailand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D016207:Cytokines; C573415:IFNG protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma