Similarly, in vitro experiments revealed that exposure of human PBMCs to high levels of IL-6, such as those typically present in sJIA, inhibits NK cell cytotoxicity by down-regulating the expression of perforin and granzyme B. Altogether, this evidence suggests that high circulating levels of IL-6 in JIA patients, besides their role in increasing macrophage activation and TLR response, play a major role in inducing a transitory defect in cytotoxicity on top of a subclinical genetic defect. This evidence concerns the gene IL6 and juvenile idiopathic arthritis.