Abstract
Trauma results in concomitant immunosuppression and elevated monocyte (MØ) inflammatory cytokine levels. The augmenting or ameliorating effect of IL-10 in septic complications after trauma is controversial. Here, IL-10 levels of trauma patients' and normals' PBMC, isolated MØ, and isolated T cells were assessed and correlated to their PBMC mitogen responses, their T-cell proliferation in an APC independent system, and their MØ production of elevated TNF-α levels. Trauma patients with depressed PBMC responses to PHA stimulation also had significantly decreased IL-10 levels in their stimulated PBMC supernates (P=0.0022) and their MDP-stimulated isolated MØ population (P=0.0004). However, patients with depressed PHA responses could have either normal or depressed T-cell proliferation in an anti-CD3-, anti-CD4-stimulated system. If APC-independent T-cell proliferation was depressed, induced IL-10 levels were suppressed (P=0.007). However, if APC-independent T-cell proliferation was normal or elevated, IL-10 levels could be normal or elevated (P=0.018). Decreased IL-10 levels correlated with depressed mitogen responses and depressed T-cell proliferation. IL-10, therefore, could not be inducing trauma patients' immunosuppression. Patients with elevated MØ TNF-α levels had depressed MØ IL-10 levels.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Waydhas C, Nast-Kolb D, Jochum M, Trupka A, Lenk S, Fritz H, Duswald K-H, Schweiberer L: Inflammatory mediators, infection, sepsis, and multiple organ failure after severe trauma. Arch Surg 127:460–467, 1992
Waage A, Aasen AO: Different role of cytokine mediators in septic shock related to meningococcal disease and surgery/polytrauma. Immunol Rev 127:221–230, 1992
Bitterman H, Kinarty A, Lazarovich H, Lahat N: Acute release of cytokines is proportional to tissue injury induced by surgical trauma and shock in rats. J Clin Immunol 11:184–192, 1991
Cavaillon J-M, Munoz C, Fitting C, Misset B, Carlet J: Trends in shock research. Circulating cytokines: The tip of the iceberg? Circ Shock 38:145–152, 1992
Suter PM, Suter S, Girardin E, Roux-Lombard P, Grau GE, Dayer J-M: High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Respir Dis 145:1016–1022, 1992
Takayama T, Miller C, Szabo G: Elevated tumor necrosis factor (TNF) production concomitant to elevated prostaglandin E2 production by trauma patients' monocytes. Arch Surg 123:29–35, 1990
Molloy RG, O'Riordain M, Holzheimer R, Nestor M, Collins K, Mannick JA, Rodrick ML: Mechanism of increased tumor necrosis factor production after thermal injury. Altered sensitivity to PGE2 and immunomodulation with indomethacin. J Immunol 151:2142–2149, 1993
Miller-Graziano CL, Kodys K, Jhaver K: MØ cell-associated TNFα is resistant to PGE2 downregulation. Circ Shock Suppl 2:68, 1993
Guillou PJ: Biological variation in the development of sepsis after surgery or trauma. Lancet 342:217–220, 1993
Markewitz A, Faist E, Niesel Th, Lang S, Weinhold Ch, Reichart B: Changes in lymphocyte subsets and mitogen responsiveness following open-heart surgery and possible therapeutic approaches. Thorac Cardiovasc Surg 40:14–18, 1992
Gadd MA, Hansbrough JF: Postburn suppression of murine lymphocyte and neutrophil functions is not reversed by prostaglandin blockade. J Surg Res 48:84–90, 1990
Teodorczyk-Injeyan JA, Sparkes BG, Lalani S, Peters WJ, Mills GB: IL-2 regulation of soluble JL-2 receptor levels following thermal injury. Clin Exp Immunol 90:36–42, 1992
Miller CL, Baker CC: Changes in lymphocyte activity after thermal injury. The role of suppressor cells. J Clin Invest 63:202–210, 1979
Gerard C, Bruyns C, Marchant A, Abramowicz D, Vandenabeele P, Delvaux A, Fiers W, Goldman M, Velu T: Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J Exp Med 177:547–550, 1993
Howard M, Muchamuel T, Andrade S, Menon S: Interleukin 10 protects mice from lethal endotoxemia. J Exp Med 177:1205–1208, 1993
Bean A, Freiberg R, Andrade S, Menon S, Zlotnik A: IL-10 and/or IL-4 protect mice against staphylococcal enterotoxin B (SEB) induced lethal shock. J Immunol 150:8, 1993
Abraham E, Chang Y-H: Haemorrhage-induced alterations in function and cytokine production of T cells and T cell subpopulations. Clin Exp Immunol 90:497–502, 1992
Ayala A, Lehman PL, Herdon CD, Chaudry IH: Interleukin (IL)-10 induced suppression of T-cell responses following hemorrhage (HEM) is mediated by eicosanoids. Intensive Care Med 20:S59, 1994
Moore KW, O'Garra A, De Waal Malefyt R, Vieira P, Mosmann TR: Interleukin-10. Annu Rev Immunol 11:165–190, 1993
Spits H, De Waal Malefyt R: Functional characterization of human IL-10. Int Arch Allergy Immunol 99:8–15, 1992
Yssel H, De Waal Malefyt R, Roncarolo M-G, Abrams JS, Lahesmaa R, Spits H, De Vries JE: IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. J Immunol 149:2378–2384, 1992
De Waal Malefyt R, Abrams J, Bennett B, Figdor CG, De Vries JE: Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes. J Exp Med 174:1209–1220, 1991
Cassatella MA, Meda L, Bonora S, Ceska M, Constantin G: Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1β in mediating the production of IL-8 triggered by lipppolysaccharide. J Exp Med 178:2207–2211, 1993
Kasama T, Strieter RM, Lukacs NW, Burdick MD, Kunkel SL: Regulation of neutrophil-derived chemokine expression by IL-10. J Immunol 152:3559–3569, 1994
Sieling PA, Abrams JS, Yamamura M, Salgame P, Bloom BR, Rea TH, Modlin RL: Immunosuppressive roles for IL-10 and IL-4 in human infection:In vitro modulation of T cell responses in leprosy. J Immunol 150:5501–5510, 1993
Chomarat P, Rissoan M-C, Banchereau J, Miossec P: Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med 177:523–527, 1993
Del Prete G, Carli MD, Almerigogna F, Giudizi MG, Biagiotti R, Romagnani S: Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol 150:353–360, 1993
De Waal Malefyt R, Yssel H, De Vries JE: Direct effects of IL-10 on subsets of human CD4+ T cell clones and resting T cells. Specific Inhibition of IL-2 production and proliferation. J Immunol 150:4754–4765, 1993
Taga K, Tosato G: IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol 148:1143–1148, 1992
Ralph P, Nakoinz I, Sampson-Johannes A, Fong S, Lowe D, Min H-Y, Lin L: IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J Immunol 148:808–814, 1992
Miller CL, Graziano CJ, Lim RC: Human monocyte plasminogen activator production: Correlation to altered MØ-T lymphocyte interaction. J Immunol 128:2194–2200, 1982
Miller-Graziano CL, Fink M, Wu JY, Szabo G, Kodys K: Mechanisms of altered monocyte prostaglandin E2 production in severely injured patients. Arch Surg 123:293–299, 1988
Szabo G, Miller-Graziano CL, Wu J-Y, Takayama T, Kodys K: Differential tumor necrosis factor production by human monocyte subsets. J Leukocyte Biol 47:206–216, 1990
Looney RJ, Abraham GN, Anderson CL: Human monocytes and U937 cells bear two distinct Fc receptors for IgG. J Immunol 136:1641–1647, 1986
Fox FE, Ford HC, Douglas R, Cherian S, Nowell PC: Evidence that TGF-β can inhibit human T-lymphocyte proliferation through paracrine and autocrine mechanisms. Cell Immunol 150:45–58, 1993
Geppert TD, Lipsky PE: Activation of T lymphocytes by immobilized monoclonal antibodies to CD3 regulatory influences of monoclonal antibodies to additional T cell surface determinants. J Clin Invest 81:1497–1505, 1988
Miller-Graziano CL, Szabo G, Griffey K, Mehta B, Kodys K, Catalano D: Role of elevated monocyte transforming growth factorβ (TGFβ) production in post-trauma immunosuppression. J Clin Immunol 11:95–102, 1991
De AK, Kodys K, Fairfield S, Miller-Graziano C: Relationship of post-trauma altered IL-12 and IL-10 to depressed patient mitogen responses.In Host Defense Alterations of Trauma, Shock and Sepsis—Multiorgan Failure/Immunotherapy of Sepsis, E Faist (ed). Berlin, Springer-Verlag, 1994, in press
Wanidworanun C, Strober W: Predominant role of tumor necrosis factor-α in human monocyte IL-10 synthesis. J Immunol 151:6853–6861, 1993
Marchant A, Deviere J, Byl B, de Groot D, Vincent J-L, Goldman M: Interleukin-10 production during septicemia. Lancet 343:707–708, 1994
Frei K, Lins H, Schwerdel C, Fontana A: Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed. J Immunol 152:2720–2728, 1994
Bogdan C, Paik J, Vodovotz Y, Nathan C: Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-β and interleukin-10. J Biol Chem 267:23301–23308, 1992
Szabo G, Kodys K, Miller-Graziano CL: Elevated monocyte interleukin-6 (Il-6) production in immunosuppressed trauma patients. I. Role of FcγRI crosslinking stimulation. J Clin Immunol 11:326–335, 1991
Miller-Graziano CL, Szabo G, Kodys K, Griffey K: Aberrations in post-trauma monocyte subpopulation: Role in septic shock syndrome. J Trauma 30:S86-S97, 1990
Ishida H, Hastings R, Thompson-Snipes L, Howard M: Modified immunological status of anti-IL-10 treated mice. Cell Immunol 148:371–384, 1993
Mulligan MS, Jones ML, Vaporciyan AA, Howard MC, Ward PA: Protective effects of IL-4 and IL-10 against immune complex-induced lung injury. J Immunol 151:5666–5674, 1993
Pradier O, Gérard C, Delvaux A, Lybin M, Abramowicz D, Capel P, Velu T, Goldman M: Interleukin-10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide. Eur J Immunol 23:2700–2703, 1993
Teodorczyk-Injevan JA: Activation-related T cell anergy after thermal injury. Intensive Care Med 20:S77, 1994
Szabo G, Verma B, Mandrekar P, Catalano D: Acute ethanol uptake prior to injury modulates monocyte TNFα production and mononuclear cell apoptosis. Intensive Care Med 20:S82, 1994
Hall SS: Immune therapies. IL-12 holds promise against cancer, glimmer of AIDS hope. Science 263:1685–1686, 1994
Fluckiger A-C, Garrone P, Durand I, Galizzi J-P, Banchereau J: Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes. J Exp Med 178:1473–1481, 1993
Taga K, Chretien J, Cherney B, Diaz L, Brown M, Tosato G: Interleukin-10 inhibits apoptotic cell death in infectious mononucleosis T cells. J Clin Invest 94:251–260, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miller-Graziano, C.L., De, A.K. & Kodys, K. Altered IL-10 levels in trauma patients' MØ and T lymphocytes. J Clin Immunol 15, 93–104 (1995). https://doi.org/10.1007/BF01541737
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01541737