Summary. Aim. To study the cytokine regulation of the immune response in patients with severe acute necrotic pancreatitis (ANP). Material and methods. A prospective cohort study of 22 patients with severe ANP who were treated in the clinic during 2014-2020 has been performed. We studied changes in blood cells expressing clusters CDIIa+, CD162+, CD95+, CD16+, HLA-DR+ molecules, levels of interleukins IL-2, IL-4, IL-6. The efficacy of treatment was determined by the duration of the organ failure, the level of postoperative complications and mortality. Results. Low expression of CD11a+ and CD162+ on immunocompetent cells together with two time reduction of the content of CD95+ cells was observed in patients with severe ANP, which caused a decrease in the concentration of IL-6 at the same time with a slight increase in IL-4. A permanent reduction of the content of CD11a+-, CD162+- and CD95+-leukocytes simultaneously with a drop of the concentration of IL-4 and an excessive increase in the levels of IL-2 and IL-6 was associated with a negative course of the disease. Conclusions. The imbalance of cytokine regulation of the immune response develops in patients with severe ANP. Progressive and excessive increase of plasma concentrations of IL-2 and IL-6 occurs as well as complete absence of IL-4 occurs in patients with an adverse course of the disease.