Increased serum-soluble interleukin-2 receptor in burn patients: characterization and effects on the immune system.
The consequences of high serum concentrations of the interleukin (IL)-2 receptor alpha chain (sIL-2Ralpha) in several diseases are poorly understood. The objective of this study was to determine the form of sIL-2Ralpha in burn patients and its biological role. sIL-2Ralpha was measured in 18 severely burned individuals who received nutritional support with a normal or low fat content. sIL-2Ralpha was elevated throughout the study and it was notably lower in patients fed a low fat diet. Serum IL-6 and sIL-2Ralpha significantly correlated (r = 0.74, p < 0.05) in burn patients. The presence of sIL-2Ralpha 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-2Ralpha 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-2Ralpha, recombinant sIL-2Ralpha was used in different cellular model involving IL-2. sIL-2Ralpha 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-2Ralpha, 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-2Ralpha, 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-2Ralpha in media. These results show that the large amount of sIL2-Ralpha circulating in burn patients is related to the inflammatory response. The amount of dietary fat modulates sIL2Ralpha 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-2Ralpha, although the presence of sIL-2Ralpha in serum can inhibit some IL-2 mediated response, such as the emergence of TH1 and TH2 cells.
Jobin
N
N
Centre Hospitalier de l'Université de Montréal (CHUM), Centre des Grands Brûlés, Montréal, PQ, Canada.
Garrel
D
D
Bernier
J
J
D000293:Adolescent; D000328:Adult; D002056:Burns / Q000097:blood* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004032:Diet; D004041:Dietary Fats; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008934:Mitogens; D010446:Peptide Fragments / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology
D004041:Dietary Fats; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008934:Mitogens; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma