CYTOKINE LEVELS IN ACUTE ALCOHOLIC HEPATITIS - A SEQUENTIAL STUDY

Chronic alcoholic liver disease is associated with several immunologic al alterations: depressed T-cell function, low serum gamma-interferon, and high serum tumour necrosis factor (TNF-alpha) and interleukin lev els. Therefore, macrophage activity seems to be enhanced. Some cytokin es, such as TNF-alpha, exert adverse effects on chronic alcoholic live r disease, so that protracted activation of macrophages with continuou s TNF-alpha production may aggravate alcoholic hepatitis. Based on the se facts we have sequentially determined serum levels of TNF-alpha,1 b eta interleukin (IL-1 beta), gamma-interferon and neopterin - a macrop hage product - at admission, and at the end of the first, third and si xth weeks after admission, of 43 patients affected by alcoholic hepati tis, and of 20 age matched sanitary workers as controls. Our patients showed higher levels of neopterin and lower levels of IL-1 beta and ga mma-interferon than the controls; TNF-alpha levels in our patients wer e almost significantly higher than in controls. TNF-alpha levels at ad mission were higher in the patients who died (P = 0.025). TNF-alpha an d neopterin levels showed no trend to normalization in patients who di ed, with higher levels of neopterin at first and third weeks and highe r TNF-alpha and gamma-interferon levels at first week. Using logistic regression analysis, serum TNF-alpha levels at admission showed signif icant (P = 0.045), independent effects on mortality, as well as serum neopterin (P = 0.0026) at the first week. Thus, enhanced macrophage ac tivity, measured by serum levels of TNF-alpha and neopterin seems to b e related to a worse prognosis in alcoholic hepatitis.