Highly multiplexed cytokine analysis of bronchoalveolar lavage and plasma reveals age-related dynamics and correlates of inflammation in children

Abstract

Despite the central role of cytokines in mediating inflammation that underlies a range of childhood diseases, cytokine testing remains primarily limited to research settings and surrogate markers of inflammation are often used to inform clinical diagnostic and treatment decisions. There are currently no reference ranges available for cytokines in healthy children, either systemically (in blood) or at sites of disease (such as the lung). In our study, we aimed to develop an openly accessible reference of cytokines in the airways and blood of healthy children spanning 1 to 16 years of age. We examined how cytokine concentration changes during childhood and assessed whether a core set of cytokine markers could be used to indirectly evaluate the response of a broad spectrum of inflammatory analytes. To develop our reference, a total of 78 unique analytes were measured in cell-free bronchoalveolar lavage (BAL) and plasma from 78 children. We showed that age profoundly impacts soluble immune analyte concentration in both sample types and identified a highly correlative core set of 10 analytes in BAL and 11 analytes in plasma capable of indirectly evaluating the response of up to 34 inflammatory mediators. This study addresses an urgent need to develop reference ranges for cytokines in healthy children to aid in diagnosis of disease, to determine eligibility for, and to monitor the effects of, cytokine-targeted monoclonal antibody therapy.