title: IL-2 regulation of soluble IL-2 receptor levels following thermal injury.
abstract: In the immunosuppressed burn patient serum levels of both IL-2 and a soluble form of IL-2 receptor alpha (sIL-2R alpha) 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-2R alpha in vitro in patients with major burns (n = 18, 30 to greater than 70% total body surface area). Peripheral blood mononuclear cell (PBMC) cultures from patients with highly elevated serum sIL-2R alpha, and from healthy controls (n = 12) were activated with concanavalin A (Con A) at initiation. In patients' cultures mitogen-induced increments of sIL-2R alpha levels were significantly lower. There was a significant negative correlation (r = 0.64, P less than 0.001) between a high serum sIL-2R alpha level and a decreased lectin-induced sIL-2R alpha release in vitro. Low levels of sIL-2R alpha 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-2R alpha release in some cultures. However, sIL-2R alpha 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-2R alpha production. Thus, in the burn patient, the reduced in vitro sIL-2R alpha release appears to relate to abnormalities in IL-2 production and action mediated through its functional surface receptor. Elevated levels of sIL-2R alpha in vivo may, therefore, reflect systemic activation of T lymphocytes in response to biologically active IL-2.
authors.affiliation: Department of Surgery, University of Toronto, Ontario, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Teodorczyk-Injeyan
authors.forename: B G
authors.initials: BG
authors.lastname: Sparkes
authors.forename: S
authors.initials: S
authors.lastname: Lalani
authors.forename: W J
authors.initials: WJ
authors.lastname: Peters
authors.forename: G B
authors.initials: GB
authors.lastname: Mills
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D002056:Burns / Q000276:immunology*; D018956:CD5 Antigens; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology
chemical_list: D015703:Antigens, CD; D018956:CD5 Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D007377:Interleukin-3; D015375:Receptors, Interleukin-2; D005576:Colforsin; D000001:Calcimycin; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D007213:Indomethacin