High Pulmonary Levels of IL-6 and IL-1β in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-γ Production in Response to Non-Typeable Haemophilus influenzae.
Pizzutto. Susan J SJ; Upham. John W JW; Yerkovich. Stephanie T ST; Chang. Anne B AB
Key Findings
- Children with chronic suppurative lung disease show reduced IFN‑γ production in response to NTHi.
- Higher airway levels of IL‑6 and IL‑1β are strongly associated with this reduced IFN‑γ response.
- Systemic inflammation appears limited; the main issue is local lung inflammation, not directly linked to LL‑37 levels.
Practical Outcomes
- For biohackers, the take‑away is that simply boosting LL‑37 isn’t shown to help; instead, strategies that lower lung inflammation (e.g., anti‑inflammatory diets or supplements) might support better immune responses, but the study provides no specific protocol.
Summary
Kids with chronic lung disease make less of the immune signal IFN‑γ when their blood cells see a common bacteria, and this weaker response is tied to higher levels of inflammation chemicals (IL‑6 and IL‑1β) in their lungs. The study didn’t find a clear link to the antimicrobial peptide LL‑37 and didn’t suggest any new treatments.
Abstract
Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.
Study Information
pubmed
2015
2015-06-12T00:00:00.000Z
10.1371/journal.pone.0129517
28