Innate production of interleukin-10 and tumor necrosis factor affects the risk of multiple sclerosis

Multiple sclerosis (MS) typically presents with a relapsing-remitting onset . This can be distinguished from primary progressive MS. Typical MS is char acterized by a profound inflammatory reaction in which anti-inflammatory cy cokine interleukin-10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor (TNF) may play a pivotal role. We tested the hypothesis that patient s with MS have a distinct innate cytokine production that contributes to th e susceptibility for and outcome of MS. The innate cytokine production of p atients was estimated as the average production of cytokines in lipopolysac charide -stimulated whole-blood cultures of 2 to 5 first-degree heathy fami ly members. A total of 126 family members of 50 patients with typical MS, 6 1 family members of 25 patients with primary progressive MS, and 129 contro l subjects of 54 families were enrolled in this study. We found that member s of families with low IL-10 and high TNF production had a fourfold increas ed risk of developing typical MS compared with members of families with hig h IL-10 and low TNF production. Patients with MS were eightfold more likely to develop typical MS than primary progressive MS when they belonged to fa milies with low IL-10 and high TNF production. The presence of human leukoc yte antigen-DR2 was associated with MS but not with TNF production. This st udy shows that typical MS is associated with an innate pro-inflammatory cyt okine profile in contrast to primary progressive MS.