IL-2 regulation of soluble IL-2 receptor levels following thermal injury

J. A. Teodorczyk-Injeyan, B. G. Sparkes, S. Lalani, W. J. Peters, G. B. Mills

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    17 Scopus citations

    Abstract

    In the immunosuppressed burn patient serum levels of both IL-2 and a soluble form of IL-2 receptor alpha (sIL-2Rα) 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-2Rα in vitro in patients with major burns (n = 18, 30 to >70% total body surface area). Peripheral blood mononuclear cell (PBMC) cultures from patients with highly elevated serum sIL-2Rα, and from healthy controls (n = 12) were activated with concanavalin A (Con A) at initiation. In patients' cultures mitogen-induced increments of sIL-2Rα levels were significantly lower. There was a significant negative correlation (r = -0.64, P < 0.001) between a high serum sIL-2Rα level and a decreased lectin-induced sIL-2Rα release in vitro. Low levels of sIL-2Rα 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-2Rα release in some cultures. However, sIL-2Rα 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-2Rα production. Thus, in the burn patient, the reduced in vitro sIL-2Rα release appears to relate to abnormalities in IL-2 production and action mediated through its functional surface receptor. Elevated levels of sIL-2Rα in vivo may, therefore, reflect systemic activation of T lymphocytes in response to biologically active IL-2.

    Original languageEnglish (US)
    Pages (from-to)36-42
    Number of pages7
    JournalClinical and Experimental Immunology
    Volume90
    Issue number1
    StatePublished - Jan 1 1992

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    Keywords

    • Burn immunosuppression
    • IL-2
    • IL-2 receptor
    • T cell activation

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Teodorczyk-Injeyan, J. A., Sparkes, B. G., Lalani, S., Peters, W. J., & Mills, G. B. (1992). IL-2 regulation of soluble IL-2 receptor levels following thermal injury. Clinical and Experimental Immunology, 90(1), 36-42.