IL-23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 has proinflammatory activity, inducing IL-17 secretion from activated CD4+ T cells and stimulating the proliferation of memory CD4+ T cells. We investigated the pathogenic role of IL-23 in CD4+ T cells in mice lacking the IL-1R antagonist (IL-1Ra−/−), an animal model of spontaneous arthritis. IL-23 was strongly expressed in the inflamed joints of IL-1Ra−/− mice. Recombinant adenovirus expressing mouse IL-23 (rAd/mIL-23) significantly accelerated this joint inflammation and joint destruction. IL-1β further increased the production of IL-23, which induced IL-17 production and OX40 expression in splenic CD4+ T cells of IL-1Ra−/− mice. Blocking IL-23 with anti-p19 Ab abolished the IL-17 production induced by IL-1 in splenocyte cultures. The process of IL-23-induced IL-17 production in CD4+ T cells was mediated via the activation of Jak2, PI3K/Akt, STAT3, and NF-κB, whereas p38 MAPK and AP-1 did not participate in the process. Our data suggest that IL-23 is a link between IL-1 and IL-17. IL-23 seems to be a central proinflammatory cytokine in the pathogenesis of this IL-1Ra−/− model of spontaneous arthritis. Its intracellular signaling pathway could be useful therapeutic targets in the treatment of autoimmune arthritis.

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This study was conducted to estimate the socioeconomic costs of overweight and obesity in a sample of Korean adults aged 20 yr and older in 2005. The socioeconomic costs of overweight and obesity include direct costs (inpatient care, outpatient care and medication) and indirect costs (loss of productivity due to premature deaths and inpatient care, time costs, traffic costs and nursing fees). Hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, stroke, colon cancer and osteoarthritis were selected as obesity-related diseases. The population attributable fraction (PAF) of obesity was calculated from national representative data of Korea such as the National Health Insurance Corporation (NHIC) cohort data and the 2005 Korea National Health and Nutrition Examination Survey (KNHANES) data. Direct costs of overweight and obesity were estimated at approximately U$1,081 million equivalent (men: U$497 million, women: U$584 million) and indirect costs were estimated at approximately U$706 million (men: U$527 million, women: U$178 million). The estimated total socioeconomic costs of overweight and obesity were approximately U$1,787 million (men: U$1,081 million, women: U$706 million). These total costs represented about 0.22% of the gross domestic product (GDP) and 3.7% of the national health care expenditures in 2005. We found the socioeconomic costs of overweight and obesity in Korean adults aged 20 yr and older are substantial. In order to control the socioeconomic burden attributable to overweight and obesity, effective national strategies for prevention and management of obesity should be established and implemented.