CYTOKINE LEVELS IN ACUTE ALCOHOLIC HEPATITIS - A SEQUENTIAL STUDY

Chronic alcoholic liver disease is associated with several immunological alterations: depressed T-cell function, low serum gamma-interferon, and high serum tumour necrosis factor (TNF-alpha) and interleukin levels. Therefore, macrophage activity seems to be enhanced. Some cytokines, such as TNF-alpha, exert adverse effects on chronic alcoholic liver disease, so that protracted activation of macrophages with continuous TNF-alpha production may aggravate alcoholic hepatitis. Based on these facts we have sequentially determined serum levels of TNF-alpha,1 beta interleukin (IL-1 beta), gamma-interferon and neopterin - a macrophage product - at admission, and at the end of the first, third and sixth weeks after admission, of 43 patients affected by alcoholic hepatitis, and of 20 age matched sanitary workers as controls. Our patients showed higher levels of neopterin and lower levels of IL-1 beta and gamma-interferon than the controls; TNF-alpha levels in our patients were almost significantly higher than in controls. TNF-alpha levels at admission were higher in the patients who died (P = 0.025). TNF-alpha and neopterin levels showed no trend to normalization in patients who died, with higher levels of neopterin at first and third weeks and higher TNF-alpha and gamma-interferon levels at first week. Using logistic regression analysis, serum TNF-alpha levels at admission showed significant (P = 0.045), independent effects on mortality, as well as serum neopterin (P = 0.0026) at the first week. Thus, enhanced macrophage activity, measured by serum levels of TNF-alpha and neopterin seems to be related to a worse prognosis in alcoholic hepatitis.