title: Children with chronic suppurative lung disease have a reduced capacity to synthesize interferon-gamma in vitro in response to non-typeable Haemophilus influenzae.
abstract: Chronic suppurative lung disease (CSLD) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. The aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly isolated from the airways in CSLD, we examined immune responses to this organism in 80 age-stratified children with CSLD and compared their responses with 51 healthy control children. Cytokines involved in the generation and control of inflammation (IFN-γ, IL-13, IL-5, IL-10 at 72 hours and TNFα, IL-6, IL-10 at 24 hours) were measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. We also measured circulating IgG subclass antibodies (IgG1 and IgG4) to two H. influenzae outer membrane proteins, P4 and P6. The most notable finding was that PBMC from children with CSLD produced significantly less IFN-γ in response to NTHi than healthy control children whereas mitogen-induced IFN-γ production was similar in both groups. Overall there were minor differences in innate and humoral immune responses between CSLD and control children. This study demonstrates that children with chronic suppurative lung disease have an altered systemic cell-mediated immune response to NTHi in vitro. This deficient IFN-γ response may contribute to increased susceptibility to NTHi infections and the pathogenesis of CSLD in children.
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Brinkin, Northern Territory, Australia.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Pizzutto
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Brinkin, Northern Territory, Australia; Queensland Lung Transplant Service, The Prince Charles Hospital, Chermside, Queensland, Australia; School of Medicine, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Yerkovich
authors.affiliation: School of Medicine, The University of Queensland, St Lucia, Queensland, Australia; Department of Respiratory Medicine, Princess Alexandra Hospital, Wooloongabba, Queensland, Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: Upham
authors.affiliation: Telethon Kids Institute, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Hales
authors.affiliation: Telethon Kids Institute, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Thomas
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Brinkin, Northern Territory, Australia; The Department of Respiratory Medicine, Royal Children's Hospital, Herston, Queensland, Australia; Queensland Children's Medical Research Institute, Royal Children's Hospital, Herston, Queensland, Australia.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Chang
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D000918:Antibody Specificity; D002648:Child; D002908:Chronic Disease; D004198:Disease Susceptibility; D005260:Female; D006193:Haemophilus influenzae / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D008171:Lung Diseases / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D008297:Male
chemical_list: D000907:Antibodies, Bacterial; D007371:Interferon-gamma
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