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Chemokines and alcoholic hepatitis: are chemokines good therapeutic targets?
  1. Bin Gao,
  2. Mingjiang Xu
  1. Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Dr Bin Gao, Laboratory of Liver Diseases, NIAAA/NIH, 5625 Fishers Lane, Bethesda, MD 20892, USA; bgao{at}mail.nih.gov

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Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease that is associated with high mortality. Despite extensive research on AH over the last several decades, the pathogenesis of AH remains largely unknown, and there are no approved targeted therapies. Inflammation (neutrophil infiltration) is generally believed to play an important role in the pathogenesis of AH; however, the mechanisms underlying neutrophil infiltration in AH and the functions of neutrophils in AH are not fully understood.1 Despite its obscure role, inflammation has been actively investigated as a therapeutic target for the treatment of AH. For example, corticosteroids, which are broadly immunosuppressive drugs, have been widely used for AH therapy for more than five decades. However, the results have been controversial. It is generally accepted that corticosteroid therapy improves short-term, but not long-term, survival rates in patients with severe AH.2

Recently, we have demonstrated that treatment with prednisolone, a synthetic steroid drug, reduced hepatotoxin (eg, ethanol and CCl4)-induced liver injury in mice by inhibiting neutrophil-mediated phagocytosis and liver regeneration, suggesting a detrimental effect of steroid therapy in hepatotoxin-induced hepatitis.3 Additionally, it is known that steroid therapy is ineffective and, occasionally, even detrimental for the treatment of neutrophil-mediated diseases because steroid treatment stimulates bone marrow neutrophil release and increases neutrophil survival.4 Based on this phenomenon, it is plausible to speculate that steroid therapy for AH may have no beneficial effects on the injured liver itself but may retain certain beneficial effects in attenuating systemic inflammatory responses and, thus, improving the short-term survival rate. Therefore, there …

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