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.

This study is the first to investigate the association between the systemic cell-mediated immune response and airway inflammation in children with CSLD. Our study of 70 children found that a reduced capacity for systemic NTHi-specific IFN-γ production was significantly associated with heightened airway inflammation as shown by high concentrations of IL-1β and IL-6 in BAL fluid. We found limited evidence of systemic inflammation in this cohort and neither markers of systemic inflammation or clinical markers of CSLD severity (including radiological scores of bronchiectasis and socio-demographic factors) predicted the capacity of the systemic NTHi-specific cell-mediated immune response. These data support the hypothesis that systemic adaptive immune responses are linked to persistent airway inflammation in children susceptible to lower respiratory infections. The primary strength of our study is the inclusion of a relatively large number of young children with lung samples. There are few such published studies and none in children. Childbased studies are important, as in adult studies of chronic infection it is difficult to know if the measured immune responses are cause or effect. Our earlier study [8] documented a log-fold increase in IFN-γ production between healthy controls aged <18 months compared to those >18 months, consistent with normal maturation of the Th1 response through early childhood. However, in the CSLD group, we found a significantly lower capacity for IFN-γ production over the same age dynamic. Thus, early childhood studies, such as ours, may provide critical information regarding inflammation and the development of the adaptive immune response.