Interleukin-2 secretion and transmembrane signalling in burned patients.
IL2 secretion in response to the T-cell mitogen Staphylococcal protein A (SPA) is significantly decreased in patients with major burns (n = 10, greater than 20% total body surface area) up to 50 days postburn in comparison with normal control (greater than 2 to 10 U/ml and 16 to 36 U/ml, respectively). Activation of protein kinase C (PK-C) and changes in [Ca++]i are both normally implicated in the production of IL2. Bypassing the requirements for mitogen-induced increases in [Ca++]i, using the cation ionophore A23187, or activating PK-C with the phorbol ester 12-o-tetradecanoyl-phorbol-13-acetate (TPA), failed to significantly restore SPA-induced IL2 production in cell cultures from burned patients. The combination of A23187 and TPA significantly (p less than 0.005-0.001) enhanced IL2 secretion in patients' cell cultures (range, 20 to greater than 64 U/ml). However, the levels of IL2 from the burned patients' cultures remained significantly lower (p less than 0.05) than those in control cultures exposed to TPA and A23187 (range, 256 to greater than 600 U/ml). Therefore, the burn-related defect in mitogen-induced IL2 secretion is only partially bypassed with cation ionophores and phorbol esters. This suggests that the abnormality in IL2 production may not be solely related to changes in PK-C activation and in [Ca++]i but may reside in other than transmembrane signalling mechanisms required for IL2 production.
D000328:Adult; D000368:Aged; D002056:Burns / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2; D013205:Staphylococcal Protein A / Q000494:pharmacology; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D013205:Staphylococcal Protein A; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium