Endogenous IL-6 protects exocrine gland integrity and restrains Th1 immune responses in a mouse model of primary Sjögren’s syndrome (HUM7P.309)

Abstract

Abstract IL-6 is a multi-functional cytokine that can either promote or suppress tissue inflammation depending on specific disease context. Previous reports showed that IL-6 is elevated in exocrine glands and sera of patients with Sjögren’s syndrome (SS), a prevalent systemic autoimmune disease primarily affecting tear and saliva secretion. However, the particular function of IL-6 in the SS disease setting is not defined. Here we show that IL-6 levels were increased during the development SS-like disease in C57BL/6.NOD-Aec1Aec2 mice, a well-defined model of primary SS. Interestingly, in vivo neutralization of endogenous IL-6 led to enhanced tissue apoptosis, leukocytic infiltration and Th1 immune responses in salivary and lacrimal glands. The tissue protective effect of IL-6 was also demonstrated in an anti-CD3 antibody-induced multi-organ inflammation model, as neutralization of IL-6 enhanced, whereas administration of IL-6 inhibited tissue apoptosis and caspase-3 activation in both salivary and lacrimal glands. Preliminary molecular analyses showed that the pro-survival effect of IL-6 was associated with altered Bcl-xL and Mcl-1 gene expression in the exocrine glands. Thus, IL-6 exerts tissue-protective and anti-inflammatory effects on exocrine tissues under inflammatory conditions such as primary SS, demonstrating the complex, tissue- and disease-specific function of IL-6 and the possibility of developing new therapies for SS by manipulating IL-6 expression or function.