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Interleukin-6: a therapeutic Jekyll and Hyde in gastrointestinal and hepatic diseases
  1. Silvio Danese1,
  2. Bin Gao2
  1. 1IBD Research Unit, Division of Gastroenterology, Istituto Clinico Humanitas, Rozzano, Milan, Italy
  2. 2Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Silvio Danese, IBD Research Unit, Istituto Clinico Humanitas, Viale Manzoni 56, Rozzano, Milan 20089, Italy; sdanese{at}hotmail.com

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Introduction

Interleukin-6 (IL-6) was discovered and cloned in 1986. Its receptor IL-6R (CD126) has an unusual organisation, consisting of two proteins: an 80 kDa IL-6 receptor and a 130 kDa signal transducer (gp130). IL-6 and its receptor interact to form a complex consisting of two IL-6 molecules plus two IL-6 receptor proteins and two gp130 proteins. The dimerised gp130 then transduces the signals, a process known as trans-signalling. In addition, a soluble IL-6 receptor also exists and exerts an agonistic effect in complex with IL-6 and can couple with the gp130 to effect transduction. Activation of gp130 leads to activation of JAK kinases and phosphorylation of STAT3, which is translocated to the nucleus and leads to gene expression.1 However, STAT3 also negatively regulates IL-6 signalling by inducing suppressor of cytokine signalling 3 (SOCS3) that in turns inhibits JAK kinase.1

IL-6 is critically involved in both acute and chronic inflammation. At the beginning of acute inflammation, it plays a key role being the main inducer of acute phase reactants such as C-reactive protein, fibrinogen and serum amyloid A protein. When its activity as a proinflammatory cytokine persists, acute inflammation turns into chronic inflammation that includes immune responses. In particular, IL-6 has a detrimental role that favours mononuclear cell accumulation at sites of injury through MCP-1 production, angioproliferation, anti-apoptotic function on T cells and in promoting Th-17 cell differentiation.2 A large number of studies have demonstrated that IL-6 is over-produced in several diseases, and it plays a fundamental role in …

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