CISH and arthritic joint disease: We hypothesized that if arthritis becomes hyper-responsive to LPS, which is a component of Gram-negative bacteria, this hyper-responsiveness may increase the levels of circulating inflammatory cytokines such as TNF, interferon-gamma (IFN-γ), and IL-6 and result in the blocking of the IL-18Rα-mediated signaling pathway by SOCS, and ultimately an amelioration of the LPS-induced arthritis.