Abstract
In this study we investigated the serum levels of a released soluble form of the interleukin-2 receptor (sIL-2R) in 42 patients with rheumatoid arthritis and in 12 cases of systemic lupus erythematosus. Data were evaluated in relationship to the clinical phase and compared with those observed in normal controls (N=56) and in osteoarthritis (N = 7). Increased levels were observed in both rheumatoid arthritis (mean ± SE, 604±49 U/ml) and systemic lupus erythematosus (1438±481 U/ml). These values were significantly higher than in control (256±15 U/ml;P<0.001) and in osteoarthritis (298±33 U/ml;P<0.001) groups. In addition, the highest values were associated with the active phases of both rheumatoid arthritis (active vs inactive, 771±78 vs 451±39 U/ml;P<0.001) and systemic lupus erythematosus (active vs inactive, 2108±489 vs 499±75 U/ml;P<0.001). Our findings suggest that the detection of sIL-2R in rheumatoid arthritis and in systemic lupus erythematosus may represent a good marker of disease activity, which indirectly indicates the ongoing activation and/or proliferation of immunoreactive cells which are involved in the pathogenetic events of these autoimmune conditions.
Similar content being viewed by others
References
Shoenfeld Y, Schwartz RS: Immunologic and genetic factors in autoimmune diseases. N Engl J Med 311:1019–1029, 1984
Decker JL, Malone DG, Haraoui B, Wahl SM, Schrieber L, Klippel JH, Steinberg AD, Wilder RL: Rheumatoid arthritis: Evolving concepts of pathogenesis and treatment. Ann Intern Med 10:810–824, 1984
Zvaifler NJ: Immunopathology of inflammatory diseases. Rheumatoid arthritis as an example. Adv Inflamm Res 7:1–11, 1984
Theofilopoulus NA, Dixon FJ: Murine models of systemic lupus erythematosus. Adv Immunol 37:269–390, 1985
Janossy G, Duke O, Poulter LW, Panayi G, Boffil M, Goldstein G: Rheumatoid arthritis: A disease of T-lymphocyte/macrophage immunoregulation. Lancet 2:839–842, 1981
Alcocer-Varela J, Alarcon-Segovia D: Decreased production of and response to interleukin 2 by cultured lymphocytes from systemic lupus crythematosus. J Clin Invest 69:1388–1392, 1982
Miyasaka N, Nakamura T, Russel IJ, Talal N: Interleukin 2 deficiencies in rheumatoid arthritis and systemic lupus erythematosus. Clin Immunol Immunopathol 31:109–117, 1984
Murakava Y, Takada S, Ueda Y, Suzuki N, Hoshino T, Sakane T: Characterization of T lymphocyte subpopulations responsible for deficient interleukin 2 activity in patients with systemic lupus erythematosus. J Immunol 134:187–195, 1985
Combe B, Pope RM, Fischbach M, Darnell B, Baron S, Talal N: Interleukin 2 in rheumatoid arthritis: Production of and response to interleukin 2 in rheumatoid synovial fluid, synovial tissue and peripheral blood. Clin Exp Immunol 59:520–528, 1985
Dauphinee MJ, Kipper SB, Wofsy D, Talal N: Interleukin-2 deficiency is a common feature of autoimmune mice. J Immunol 127:2483–2487, 1981
Altman A, Theofilopoulos AN, Weiner R, Katz DH, Dixon FJ: Analysis of T cell function in autoimmune murine strains. Defects in production of and responsiveness to interleukin 2. J Exp Med 154:791–808, 1981
Cantrell DA, Smith K: The interleukin 2 T cell system. A new cell growth model. Science 224:1312–1316, 1984
Robb RJ, Greene WC, Rusk CM: Low and high affinity cellular receptor for interleukin 2. Implication for the level of Tac antigen. J Exp Med 160:1126–1146, 1985
Tsudo M, Uchiyama T, Uchino H: Expression of Tac antigen on activated normal human B cells. J Exp Med 160:612–617, 1984
Herrmann F, Cannistra M, Levine H, Griffin JD: Expression of interleukin 2 by gamma interferon-induced human leukemic and normal monocyte cells. J Exp Med 162:1111–1116, 1985
Greene WC, Leonard WJ, Depper JM, Nelson DL, Waldmann TA: The human interleukin-2 receptor: Normal and abnormal expression in T cells and in leukemias induced by the human T-lymphotropic retroviruses. Ann Intern Med 105:560–572, 1986
Smith KA: The bimolecular structure of the interleukin 2 receptor. Immunol Today 9:36–37, 1988
Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL: Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 135:3172–3177, 1985
Osawa H, Josimovic-Alasevic O, Diamatstein T: Interleukin 2 receptors are released by cells in vitro and in vivo. I. Detection of soluble IL2 receptors in cell culture supernatants and in the serum of mice by an immunoradiometric assay. Eur J Immunol 16:467–469, 1986
Rubin LA, Jay G, Nelson DL: The released interleukin-2 receptor binds interleukin-2 efficiently. J Immunol 137:3841–3844, 1986
Nelson DL, Rubin LA, Kurman CC, Fritz ME, Boutin B: An analysis of the cellular requirements for the production of soluble interleukin-2 receptors in vitro. J Clin Immunol 6:114–120, 1986
Pizzolo G, Chilosi M, Semenzato G: Annotation. The soluble interleukin-2 receptor in haematological disorders. Br J Haematol 67:377–380, 1987
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arth Rheum 25:1271–1277, 1982
Ropes MV, Bennet GA, Cobb S, Jacox R, Jessar RA: 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175–176, 1958
Veyes EM, Hermanns P, Verbruggen G, Schindler J, Goldstein G: Evaluation of T cell subsets with monoclonal antibodies in synovial fluid in rheumatoid arthritis. J Rheumatol 9:821–826, 1982
Chilosi M, Semenzato G, Cetto G, Ambrosetti A, Fiore-Donati L, Perona G, Berton G, Lestani M, Scarpa A, Agostini C, Trentin L, Zambello R, Masciarelli M, Dazzi F, Caligaris-Cappio F, Pizzolo G: Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: Relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity. Blood 70:1530–1535, 1987
Balderas RS, Josimovic-Alasevic O, Diamatstein T, Dixon FJ. Theofilopoulos AN: Elevated titers of cell-free interleukin 2 receptor in serum of lupus mice. J Immunol 139:1496–1500, 1987
Katz P, Zaytonu A, Lee JA, Pannush RS, Longley S: Abnormal natural killer cell activity in systemic lupus erythematous: An intrinsic defect in the lytic event. J Immunol 129:1966–1971, 1982
Emery P, Panayi GS, Nouri AM: Interleukin-2 reverses deficient cell-mediated immune responses in rheumatoid arthritis. Clin Exp Immunol 57:123–129, 1984
Tsokos GC, Smith PL, Christian CB, Lipnick RL, Balow JE, Djeu JY: Interleukin-2 restores the depressed allogenic cell mediated lympholysis and natural killer cell activity in patients with systemic lupus erythematosus. Clin Immunol Immunopathol 34:379–386, 1985
Pizzolo G, Chilosi M, Vinante F, Dazzi F, Lestani M, Perona G, Benedetti F, Todeschini G, Vincenzi C, Trentin L, Semenzato G: Soluble interleukin-2 receptors in the serum of patients with Hodgkin's disease. Br J Cancer 55:427–428, 1987
Semenzato G, Foà R, Agostini C, Zambello R, Trentin L, Vinante F, Benedetti F, Chilosi M, Pizzolo G: High levels of soluble interleukin-2 receptor in patients with B chronic lymphocytic leukemia. Blood 70:396–400, 1987
Lawrence EC, Berger MB, Brousseau KP, Rodriquez TM, Siegel SJ, Kurman CC, Nelson DL: Elevated serum levels of soluble interleukin-2 receptors in active pulmonary sarcoidosis: Relative specificity and association with hypercalcemia. Sarcoidosis 4:87–93, 1987
Colvin RB, Fuller TC, MacKeen L, Kung PC, Ip SH, Cosimi AB: Plasma interleukin 2 receptor levels in renal allograft recipients. Clin Immunol Immunopathol 43:273–276, 1987
Alberti A, Chemello L, Fattovich G, Semenzato G, Vinante F, Pizzolo G: Soluble interleukin 2 receptors in serum of patients with acute and chronic viral hepatitis (submitted for publication).
Burmester GR, Jahn B, Gramatzki M, Zacker J, Kalden JR: Activated T cells in vivo and in vitro: Divergence in expression of Tac and Ia antigens in the nonblastoid small T cells of inflammation and normal T cells activated in vitro. J Immunol 133:1230–1234, 1984
Waalen K, Foore O, Linker-Israeli M, Thoen J: Evidence of an activated T-cell system with augmented turnover of interleukin 2 in rheumatoid arthritis. Stimulation of human T lymphocytes by dendritic cells as a model for rheumatoid T cell activation. Scand J Immunol 25:367–373, 1987
Damle NK, Childs AL, Doyle LV: Immunoregulatory T lymphocytes in man. Soluble antigen-specific suppressor-inducer T lymphocytes are derived from the CD4+CD45R-p80+ subpopulation. J Immunol 139:1501–1508, 1987
Goto M, Miyamoto T, Nishioka K, Uchida S: T cytotoxic and helper cells are markedly increased, and T suppressor and inducer cells are markedly decreased, in rheumatoid synovial fluids. Arthr Rheum 30:737–743, 1987
Pitzalis C, Kingsley G, Murphy J, Panayi G: Abnormal distribution of the helper-inducer T-lymphocyte subsets in the rheumatoid joints. Clin Immunol Immunopathol 45:252–258, 1987
Cupps TR, Fauci AS: Corticosteroid-mediated immunoregulation in man. Immunol Rev 65:133–155, 1982
Arya SK, Wong-Staal F, Gallo RC: Dexamethasone-mediated inhibition of human T cell growth factor and y-interferon messenger RNA. J Immunol 133:273–276, 1984
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Semenzato, G., Bambara, L.M., Biasi, D. et al. Increased serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and rheumatoid arthritis. J Clin Immunol 8, 447–452 (1988). https://doi.org/10.1007/BF00916949
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00916949