We read with interest the article by Lemmers and colleagues recently published in HEPATOLOGY elegantly demonstrating that interleukin-17 (IL-17) may be pathogenically important in human alcoholic liver disease (ALD).1 The authors reported that IL-17 plasma levels were markedly raised in patients with alcoholic hepatitis and that peripheral blood cells disclosed an IL-17–secreting phenotype in this clinical entity. Additionally, liver infiltration with IL-17–secreting cell infiltrates seems to be a pathological hallmark of patients with ALD.1 Although the cornerstone for therapy for ALD remains lifestyle modification, the interesting question raised by the study of Lemmers et al. is whether targeting IL-17 might be a potential therapeutic strategy in alcoholic hepatitis.
Here, we put forward a few possibilities that might be explored in this research area.
First, a potential approach to inhibiting IL-17 signaling may be represented by the stimulation of retinoic acid receptor α, using all-trans retinoic acid (ATRA).2 Accordingly, animal studies have shown that ATRA can inhibit the differentiation of the effector T cell lineage Th-17 by promoting transforming growth factor-β signaling.3 Of note, ATRA has been already proven to be potentially useful for treatment of chronic hepatitis C,4 but no data are not yet available for its use in ALD. An alternative approach might be represented by supplementation with essential omega-3 fatty acids, which have a demonstrated IL-17–decreasing effect5 and whose potential usefulness to slow down liver injury has been already suggested.6 Of interest is also the observation that some therapies currently used in ALD are also capable of acting on the IL-17 pathway. In this regard, corticosteroids, which are effective in selected patients with alcoholic hepatitis,7 have been shown to reduce IL-17 expression.8 Additionally, anti–tumor necrosis factor-α therapy, which has been suggested for some patients with ALD,7 can exert significant IL-17–decreasing effects.5
In summary, the authors are to be congratulated for having performed an interesting study that might stimulate research in IL-17–targeted treatment of ALD. Hopefully this can ultimately improve the quality of life of these patients and, in some cases, even decrease short-term mortality.