Blood neutrophil functions and cytokine release in severe alcoholic hepatitis: effect of corticosteroids

Abstract

Background/Aims: Several observations point to an important role of interactions between polymorphonuclear neutrophils and cytokines in severe alcoholic hepatitis. The polymorphonuclear neutrophil activation status and the local and systemic pro- and anti-inflammatory cytokine responses were quantified. The effect of corticosteroids, widely used in this setting, was evaluated using these parameters. Methods: We studied blood polymorphonuclear neutrophil functions in terms of L-selectin and β2-integrin expression, H 2O 2 production and IL-8 and tumor necrosis factor α synthesis capacity. We also measured IL-8, tumor necrosis factor α and IL-10 plasma and liver tissue levels. Fifteen patients with alcoholic hepatitis were compared to 15 patients with alcoholic cirrhosis without alcoholic hepatitis, and to 10 healthy volunteers. The impact of a 28-day course of corticosteroids on blood neutrophils activation status and cytokine levels was evaluated in patients with alcoholic hepatitis. Results: Blood polymorphonuclear neutrophils were activated, as shown by increased H 2O 2 production (48±6 vs 29±6 MFI in healthy controls), and decreased L-selectin expression (300±61 vs 449±59 in healthy controls). Upon stimulation, polymorphonuclear neutrophils synthesized large amounts of IL-8 (21.7±9.2 ng/ml vs 8.8±10 ng/ml in healthy controls) and tumor necrosis factor α (524±132 pg/ml vs 79±144 pg/ml in healthy controls). Tumor necrosis factor α and IL-8 plasma and tissue levels were markedly increased as IL-10 was barely detectable in alcoholic hepatitis patients, compared to cirrhotic patients and healthy controls. During steroid therapy, plasma levels of the pro-inflammatory cytokine IL-8 fell as early as day 14, while levels of the anti-inflammatory cytokine IL-10 increased on day 21. Finally, polymorphonuclear neutrophil functions returned to normal after treatment. Conclusion: Severe alcoholic hepatitis appears to be associated with polymorphonuclear neutrophil activation and an imbalance between pro- and anti-inflammatory cytokines; during steroid therapy a normalization of these parameters was observed.