IL-2 REGULATION OF SOLUBLE IL-2 RECEPTOR LEVELS FOLLOWING THERMAL-INJURY

In the immunosuppressed burn patient serum levels of both IL-2 and a soluble form of IL-2 receptor alpha (sIL-2Ralpha) are significantly elevated. Strikingly, the production of these markers by the in vitro activated patients' cells is decreased. This study examines the role of IL-2 in the decreased production of the sIL-2Ralpha in vitro in patients with major burns (n = 18, 30 to > 70% total body suface area). Peripheral blood mononuclear cell (PBMC) cultures from patients with highly elevated serum sIL-2Ralpha, and from healthy controls (n = 12) were activated with concanavalin A (Con A) at initiation. In patients cultures mitogen-induced increments of sIL-2Ralpha levels were significantly lower. There was a significant negative correlation (r= -0.64, P < 0.001) between a high serum sIL-2Ralpha level and a decreased lectin-induced sIL-2Ralpha release in vitro. Low levels of sIL-2Ralpha in patients' samples were not normalized by increasing the number of T lymphocytes. Also exogenous rIL-1 was without effect, whereas rIL-3 increased sIL-2Ralpha release in some cultures. However, sIL-2Ralpha levels were significantly increased in patients' cultures by (i) addition of exogenous IL-2; (ii) removal of adherent cells; (iii) addition of cyclooxygenase inhibitor, indomethacin; (iv) bypassing cell surface activation by the combination of the calcium ionophore A23187 and the phorbol ester 12-o-tetradecanoyl acetate. The cyclic AMP-elevating drug, forskolin, abrogated the ability of exogenous IL-2 to increase sIL-2Ralpha production. Thus, in the burn patient, the reduced in vitro sIL-2Ralpha release appears to relate to abnormalities in IL-2 production and action mediated through its functional surface receptor. Elevated levels of sIL-2Ralpha in vivo may, therefore, reflect systemic activation of T lymphocytes in response to biologically active IL-2.