Serum cytokines elevated during gluten‐mediated cytokine release in coeliac disease

Cytokines have been extensively studied in coeliac disease, but cytokine release related to exposure to gluten and associated symptoms has only recently been described. Prominent, early elevations in serum IL-2 after gluten support a central role for T-cell activation in the clinical reactions to gluten in coeliac disease. Establish a quantitative hierarchy of serum cytokines and their relation to symptoms in patients with coeliac disease during gluten-mediated cytokine release reactions. Sera were analyzed from coeliac disease patients on gluten free diet (n=25), and from a parallel cohort of healthy volunteers (n=25) who underwent an unmasked gluten challenge. Sera were collected at baseline, and 2, 4, and 6 hours after consuming ten grams vital wheat gluten flour. 187 cytokines were assessed. Confirmatory analyses were performed by high sensitivity electrochemiluminescence immunoassay. Cytokine elevations were correlated with symptoms. Cytokine release following gluten challenge in coeliac disease patients included significant elevations of IL-2, CCL20, IL-6, CXCL9, CXCL8, IFN-γ, IL-10, IL-22, IL-17A, TNF-α, CCL2, and amphiregulin. IL-2 and IL-17A were earliest to rise. Peak levels of cytokines were generally at four hours. IL-2 increased most (median 57-fold), then CCL20 (median 10-fold). Cytokine changes were strongly correlated with one another, and the most severely symptomatic patients had highest elevations. Early elevations of IL-2, IL-17A, IL-22 and IFN-γ after gluten in patients with coeliac disease implicates rapidly activated T cells as their likely source. Cytokine release after gluten could aid in monitoring experimental treatments and support diagnosis.