Interleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic Lupus Erythematosus-Like Disease of BXSB. Yaa Mice

IL6 is a multifunctional cytokine that drives terminal B cell differentiation and secretion of immunoglobulins. IL6 also cooperates with IL21 to promote differentiation of CD4(+) T follicular helper cells (TFH). Elevated serum levels of IL6 correlate with disease flares in patients with systemic lupus erythematosus (SLE). We previously reported that IL21 produced by T-FH plays a critical role in the development of the SLE-like disease of BXSB. Yaa mice. To examine the possible contributions of IL6 to disease, we compared disease parameters in IL6-deficient and IL6-competent BXSB. Yaa mice. We report that survival of IL6-deficient BXSB. Yaa mice was significantly prolonged in association with significant reductions in a variety of autoimmune manifestations. Moreover, B cells stimulated by co-engagement of TLR7 and B cell receptor (BCR) produced high levels of IL6 that was further augmented by stimulation with Type I interferon (IFN1). Importantly, the frequencies of T-FH and serum levels of IL21 were significantly reduced in IL6-deficient mice. These findings suggest that high-level production of IL6 by B cells induced by integrated signaling from the IFN1 receptor, TLR7 and BCR promotes the differentiation of IL21-secreting T-FH in a signaling sequence that drives the lethal autoimmune disease of BXSB. Yaa mice.Peer reviewe

Visually-guided irrigation in patients with early knee osteoarthritis: a multicenter randomized, controlled trial.

To determine if visually-guided arthroscopic irrigation is an effective therapeutic intervention in patients with early knee osteoarthritis.Ninety patients with knee osteoarthritis were randomized in a double-blind fashion to receive either arthroscopic irrigation with 3000 ml of saline (treatment group) or the minimal amount of irrigation (250 ml) required to perform arthroscopy (placebo group). The primary outcome variable was aggregate WOMAC score.The study did not demonstrate an effect of irrigation on arthritis severity as measured by aggregate WOMAC scores, the primary outcome variable; the mean change in aggregate WOMAC score at 12 months was 15.5 (95% CI 7.7, 23.4) for the full irrigation group compared to 8.9 (95% CI 4.9, 13.0) for the minimal irrigation group (P=0.10). Full irrigation did have a statistically significant effect on patients' self-reported pain as measured by the WOMAC pain subscale and by a visual analog scale (VAS) (the secondary outcome variables). Mean change in WOMAC pain scores decreased by 4.2 (95% CI -0.9, 9.4) for the full irrigation group compared with a mean decrease of 2.3 (95% CI -0.1, 4.7) in the minimal irrigation group (P=0.04). Mean VAS pain scores decreased by 1.47 (95% CI -1.2, 4.1) in the full irrigation group compared to a mean decrease of 0.12 (95% CI 0.0, 0.3) in the minimal irrigation group (P=0.02). A hypothesis-generating post-hoc analysis of the effect of positively birefrigent intraarticular crystals showed that patients with and without intraarticular crystals had statistically significant improvements in pain assessments and aggregate WOMAC scores at 12 months; patients with crystals had statistically greater improvements in pain.Visually-guided arthroscopic irrigation may be a useful therapeutic option for relief of pain in a subset of patients with knee OA, particularly in those who have occult intraarticular crystals