Interestingly, most of these proinflammatory effects of IL-6 are mediated by IL-6 transsignaling [156] as (i) protection from experimental arthritis in IL-6-deficient mice could be only restored by the injection of a fusion protein of IL-6 and the sIL-6R (hyper-IL-6), but not by IL-6 alone [157], and (ii) the treatment of experimental arthritis in wild type mice with a fusion protein consisting of the entire extracellular portion of gp130 fused to the Fc region of human IgG1 132 (sgp130) leads to a similar (protected) phenotype as observed in IL-6-deficient mice [157–159]. The gene discussed is IL6ST; the disease is arthritic joint disease.