The consequences of high serum concentrations of the interleukin (IL)-2 receptor alpha chain (sIL-2R alpha) in several diseases are poorly understood. The object-ive of this study was ro determine the form of sIL-2R alpha in burn patients and its biological role, sIL-2R alpha was measured in 18 severely burned individuals who received nutritional support with a normal or low far content. sIL-2R alpha was elevated throughout the study and it. was notably lower in patients fed a low fat diet. Serum IL-6 and sIL-2R alpha significantly correlated (r = 0.74, p < 0.05) in burn patients. The presence of sIL-2R alpha was associated with a decrease in DR molecules in the CD2(-) and CD11b(+) cells of these patients. Western blot analysis of serum protein with N-terminal or C-terminal specific antibodies indicated that sIL-2R alpha represents the extracellular domain of this molecule. Patient serum inhibited specifically murine, but not human IL-2-dependent T-cell proliferation. To determine the significance of sIL-2R alpha, recombinant sIL-2R alpha was used in different cellular model involving IL-2. sIL-2R alpha inhibited natural killer cell activity by 50% in the presence of IL-2. The basal proliferation of peripheral blood mononuclear cells was inhibited by sIL-2R alpha, but phytohemagglutinin-induced proliferation was unaffected by this form of receptor. Interferon (INF)-gamma production induced by OKT-3 on peripheral blood mononuclear cells was not altered by sIL-2R alpha, but IL-2 induced increase in INF-gamma production was suppressed. The decreasing production of INF-gamma in the presence of IL-4 was significantly increased in the presence of sIL-2R alpha in media. These results show that the large amount of sIL2-R alpha circulating in burn patients is related to the inflammatory response. The amount of dietary fat modulates sIL2R alpha concentration in burn patients, confirming the beneficial effect of low fat administration after burn trauma. Inhibition of T-cell activation in burn patients is not directly related to sIL-2R alpha, although the presence of sIL-2R alpha in serum can inhibit some IL-2 mediated response, such as the emergence of TH1 and TH2 cells. (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.