High Pulmonary Levels of IL-6 and IL-1ß in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-? Production in Response to Non-Typeable Haemophilus influenzae

Pizzutto, Susan J.; Upham, John W.; Yerkovich, Stephanie T.; Chang, Anne B.

IL1-β, produced by a variety of pulmonary cells in response to a microbial challenge, drives the inflammation cascade, localises neutrophils and promotes the production of inflammatory modulators, such as IL-6 and IP-10 production [21] . Consistent with this, we found a strong correlation between levels of BAL IL-1β, IL-6 and IP-10 in children with CSLD. IL-6 plays a complex role in the inflammatory response, from promoting inflammation to wound healing. Dysregulation of IL-6 is associated with chronic inflammation). In addition to its inflammatory modulating properties, IL-6 is integral to initiating the adaptive response and in directing its primary phenotype. In the lung, IL-6 polarises the adaptive immune response in favour of the humoral response. Animal and in vitro studies indicate this is accomplished in two ways. Firstly, dendritic cell-derived IL-6 suppresses activation of the Th1 pathway by inhibiting IL-12 production [22, 23] . Secondly IL-6, in synergy with macrophage-derive IP-10, promotes the differentiation of B-cells into antibody-producing plasma cells [24] . Minimal numbers of lymphocytes in our BAL samples precluded our ability to study airway cells directly, however our data are consistent with the hypothesis that localised immune responses may not be contained to the lungs. We found that IL-1β, IL-6 and IP-10 were positively correlated with each other. Furthermore BAL IL-1β was positively associated with BAL IL-13. An environment high in these cytokines is conducive to a polarised humoral immune response. Thus it is plausible that the low systemic capacity for NTHi-specific IFN-γ production, also associated with BAL IL-1β and IL-6, may be a reflection of prolonged humoral responses in the lungs.