Adipokines play a significant role in the pathogenesis of a low-grade inflammation associated with obesity and metabolic syndrome, and in chronic inflammatory and autoimmune diseases such as rheumatoid arthritis. Among variety of adipokines, resistin and visfatin are proposed as important pro-inflammatory mediators, which also interfere with the central regulation of insulin sensitivity. Resistin has been initially postulated as a risk factor for insulin resistance, however, the subsequent available data on it have revealed contradictory findings in both humans and rodents. On the other hand, visfatin has been suggested to be a beneficial adipokine with insulin-mimicking/-sensitizing effects, but regulation of visfatin production and its physiological importance in the conditions of obesity and type 2 diabetes mellitus are still not completely understood. Despite the opposing effects of resistin and visfatin on the regulation of insulin sensitivity, both adipokines have pro-inflammatory properties. Clinical and experimental studies have shown that the expression and secretion of resistin and visfatin are up-regulated during inflammation and in response to pro-inflammatory cytokines. It has also become increasingly evident that resistin as well as visfatin itself can contribute to the inflammatory processes by triggering cytokine production and NF-kappaB activation. New insight into the role of adipokines makes them attractive targets for novel therapeutic strategies in chronic inflammatory diseases or subclinical inflammation relating to obesity and various metabolic abnormalities.

Although pain is a common symptom of various diseases and disorders, its contribution to disease pathogenesis is not well understood. Here we show using murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), that pain induces EAE relapse. Mechanistic analysis showed that pain induction activates a sensory-sympathetic signal followed by a chemokine-mediated accumulation of MHC class II+CD11b+ cells that showed antigen-presentation activity at specific ventral vessels in the fifth lumbar cord of EAE-recovered mice. Following this accumulation, various immune cells including pathogenic CD4+ T cells recruited in the spinal cord in a manner dependent on a local chemokine inducer in endothelial cells, resulting in EAE relapse. Our results demonstrate that a pain-mediated neural signal can be transformed into an inflammation reaction at specific vessels to induce disease relapse, thus making this signal a potential therapeutic target.DOI: http://dx.doi.org/10.7554/eLife.08733.001

Impact of stress on diseases including gastrointestinal failure is well-known, but molecular mechanism is not understood. Here we show underlying molecular mechanism using EAE mice. Under stress conditions, EAE caused severe gastrointestinal failure with high-mortality. Mechanistically, autoreactive-pathogenic CD4+ T cells accumulated at specific vessels of boundary area of third-ventricle, thalamus, and dentate-gyrus to establish brain micro-inflammation via stress-gateway reflex. Importantly, induction of brain micro-inflammation at specific vessels by cytokine injection was sufficient to establish fatal gastrointestinal failure. Resulting micro-inflammation activated new neural pathway including neurons in paraventricular-nucleus, dorsomedial-nucleus-of-hypothalamus, and also vagal neurons to cause fatal gastrointestinal failure. Suppression of the brain micro-inflammation or blockage of these neural pathways inhibited the gastrointestinal failure. These results demonstrate direct link between brain micro-inflammation and fatal gastrointestinal disease via establishment of a new neural pathway under stress. They further suggest that brain micro-inflammation around specific vessels could be switch to activate new neural pathway(s) to regulate organ homeostasis.DOI: http://dx.doi.org/10.7554/eLife.25517.001