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Children with chronic suppurative lung disease have a reduced capacity to synthesize interferon-gamma in vitro in response to non-typeable Haemophilus influenzae.

Pizzutto SJ, Yerkovich ST, Upham JW, Hales BJ, Thomas WR, Chang AB - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Menzies School of Health Research, Charles Darwin University, Brinkin, Northern Territory, Australia.

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.

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Innate (24 hour) cytokine production.In vitro cytokine production by HC (open circles) and CSLD (filled circles) PBMC following 24 hour challenge with NTHi. Delta concentration (NTHi challenge minus nil challenge) with median and IQR.
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pone-0104236-g003: Innate (24 hour) cytokine production.In vitro cytokine production by HC (open circles) and CSLD (filled circles) PBMC following 24 hour challenge with NTHi. Delta concentration (NTHi challenge minus nil challenge) with median and IQR.

Mentions: Because innate immunity may modulate adaptive immunity, we examined the strength and nature of the innate immune response to NTHi by measuring IL-6, TNFα and IL-10 production in 24 hour NTHi-stimulated PBMC (figure 3). Measurable quantities of the cytokines were produced by almost all children. Children with CSLD aged18–36 months produced less IL-6 and TNFα than HC children, but these differences were not observed in the three other age groups. IL-10 production at 24 hours was similar across all groups. When all age groups were combined, the CSLD group produced less IL-6 than the HC group (median (IQR) 5527 (3131–8733) versus11425 (4835–18458) pg/ml, age-adjusted p = 0.007; table S1).


Children with chronic suppurative lung disease have a reduced capacity to synthesize interferon-gamma in vitro in response to non-typeable Haemophilus influenzae.

Pizzutto SJ, Yerkovich ST, Upham JW, Hales BJ, Thomas WR, Chang AB - PLoS ONE (2014)

Innate (24 hour) cytokine production.In vitro cytokine production by HC (open circles) and CSLD (filled circles) PBMC following 24 hour challenge with NTHi. Delta concentration (NTHi challenge minus nil challenge) with median and IQR.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128648&req=5

pone-0104236-g003: Innate (24 hour) cytokine production.In vitro cytokine production by HC (open circles) and CSLD (filled circles) PBMC following 24 hour challenge with NTHi. Delta concentration (NTHi challenge minus nil challenge) with median and IQR.
Mentions: Because innate immunity may modulate adaptive immunity, we examined the strength and nature of the innate immune response to NTHi by measuring IL-6, TNFα and IL-10 production in 24 hour NTHi-stimulated PBMC (figure 3). Measurable quantities of the cytokines were produced by almost all children. Children with CSLD aged18–36 months produced less IL-6 and TNFα than HC children, but these differences were not observed in the three other age groups. IL-10 production at 24 hours was similar across all groups. When all age groups were combined, the CSLD group produced less IL-6 than the HC group (median (IQR) 5527 (3131–8733) versus11425 (4835–18458) pg/ml, age-adjusted p = 0.007; table S1).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Menzies School of Health Research, Charles Darwin University, Brinkin, Northern Territory, Australia.

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.

Show MeSH
Related in: MedlinePlus