Blood neutrophil functions and cytokine release in severe alcoholic hepatitis: effect of corticosteroids.
OBJECTIVE
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 beta2-integrin expression, H2O2 production and IL-8 and tumor necrosis factor alpha synthesis capacity. We also measured IL-8, tumor necrosis factor alpha 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 H2O2 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 alpha (524+/-132 pg/ml vs 79+/-144 pg/ml in healthy controls). Tumor necrosis factor alpha 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.


CONCLUSIONS
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.
Taïeb
J
J
Immunology Department and INSERM U479, Bichat Hospital, Paris, France.
Mathurin
P
P
Elbim
C
C
Cluzel
P
P
Arce-Vicioso
M
M
Bernard
B
B
Opolon
P
P
Gougerot-Pocidalo
M A
MA
Poynard
T
T
Chollet-Martin
S
S
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood*; D005260:Female; D006519:Hepatitis, Alcoholic / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D019041:L-Selectin / Q000097:blood; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D019041:L-Selectin; D006861:Hydrogen Peroxide