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, > 20% total body surface area) up to 50 days postburn in comparison with normal control (> 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 < 0.005-0.001) enhanced IL2 secretion in patients’ cell cultures (range, 20 to > 64 U/ml). However, the levels of IL2 from the burned patients’ cultures remained significantly lower (p < 0.05) than those in control cultures exposed to TPA and A23187 (range, 256 to > 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.