Summary
Immunosenescence is a well known physiological phenomenon resulting from reduced efficiency of the immune system in the elderly. It has been studied both in animal models and in humans. In this review attention is focused on T cell responsiveness, since this cell type is both a marker of the immune response and one of the main targets of several drugs. For this latter reason, most studies of the effect of drugs on the immune system have been performed with reference to the effects on T lymphocytes.
In the second part of the article experimental data concerning several drugs and drug classes [steroids, calcium antagonists, theophylline, histamine H1- and H2-receptor antagonists, sodium cromoglycate (cromolyn sodium), pirenzepine, rosaprostol, β2-mimetics, antibiotics and antibacterials] and immune responsiveness are reviewed.
Lastly, the clinical perspectives of pharmacological treatment in aged subjects in relation to immunosenescence are evaluated.
Similar content being viewed by others
References
Allalouf D, Komlos L, Notmann J, Halbrecht I, Levinsky H. Sialic acid content and sialyltransferase activity in human lymphocytes with advancing age. Mechanisms of Ageing and Development 44: 45–50, 1988
Asano Y, Komuro T, Kubo M, Sano K, Tada T. Age-related degeneracy of T cell repertoire: influence of the aged environment on T cell allorecognition. Gerontology 36: 3–9, 1990
Bottazzo GF, Pujoll-Borrell R, Hanafusa T. Role of aberrant HLADR expression and antigens presentation in induction of endocrine autoimmunity. Lancet 2: 1115–1120, 1983
Canonica GW, Caria M, Venuti D, Cipro G, Ciprandi G, et al. T cell activation through different membrane structures (T3/Ti, T11, T44) and frequency analysis of proliferating and interluekin-2 producer T lymphocyte precursors in aged individuals. Mechanisms of Ageing and Development 42: 27–35, 1988a
Canonica GW, Ciprandi G. Antiallergic drugs and the immune response. Allergy 44: 1–5, 1989
Canonica GW, Ciprandi G, Bagnasco M, Scordamaglia A. Oral cromolyn in food allergy: in vivo and in vitro effects. Clinical Immunology and Immunopathology 41: 154–159, 1986a
Canonica GW, Ciprandi G, Caria M, Dirienzo W, Shums A, et al. Defect of autologous mixed lymphcoyte reaction and interleukin-2 in aged individuals. Mechanisms of Ageing and Development 32: 205–212, 1985
Canonica GW, Ciprandi G, Scordamaglia A, Caria M, Venuti D, et al. Lymphokine production and T cell proliferation in aged subjects. In Facchini A, et al. (Eds) Immunoregulation in aging, pp. 95–99, JH Pasmans Offsetdrukkerij BV, The Netherlands, 1986b
Canonica GW, Ciprandi G, Scordamaglia A, Ruffoni S, Pizzorno G, et al. Cytoprotective drugs: a new perspective in the treatment of adverse reactions to foods. Annals of Allergy 60: 541–545, 1988b
Canonica GW, Dirienzo W, Cosulich E, Ferrini S, Ciprandi G, et al. Abnormalities of circulating T cell subsets in atopy: influence of specific immunotherapy. International Archives of Allergy and Applied Immunology 71: 300–305, 1983
Canonica GW, Mingari MC, Melioli G, Colombatti M, Moretta L. Imbalance of T cell subpopulations in patients with atopic diseases and effect of specific immunotherapy. Journal of Immunology 123: 2669–2672, 1979
Canonica GW, Scordamaglia A, Bagnasco M, Ciprandi G. Drugs and the immune response: knowledge and perspectives in allergology. Annals of Allergy 62: 483–487, 1989
Chang M, Utsuyuma M, Hirokawa K, Makinodam T. Decline in the production of interleukin-3 with age in mice. Cellular Immunology 115: 1–2, 1988
Chopra R, Nagel J, Chrest F, Adler W. Impaired phorbol ester and calcium ionophore induced proliferation of T cells from old humans. Clinical and Experimental Immunology 70: 456–462, 1987
Ciprandi G, Cipro G, Paolieri F, Venuti D, Canonica GW. Oxatomide does not influence the immune response: a further support to its employment in allergic disorders. International Journal of Immunotherapy 3: 301–305, 1987
Ciprandi G, Cipro G, Paolieri F, Venuti D, Scordamaglia A, et al. Fenoterol unaffects the in vitro immune response. International Journal of Immunopharmacology 10: 463–467, 1988a
Ciprandi G, Scordamaglia A, Bagnasco M, Caria M, Dirienzo W, et al. Cromolyn’s effects on the immune systems. Diagnostic Immunology 4: 312–314, 1986a
Ciprandi G, Scordamaglia A, Ruffoni S, Pizzorno G, Canonica GW, et al. Ketotifen and treatment of adverse reactions to foods: clinical and immunological effects. Current Medical Research and Opinion 10: 346–352, 1986b
Ciprandi G, Venuti D, Ruffoni S, Cilli P, Canonica GW. In vitro immune response to two new antihistamines (astemizole and levocabastine). International Journal of Immunotherapy 4: 213–217, 1988b
Dammacco F, Miescher PA. Immunodepressive agents. In Chedid L, et al. (Eds) Advances in immunopharmacology, pp. 425–427, Pergamon Press, New York, 1986
Dirienzo W, Stefanini GF, Singh V, Pauling EE, Canonica GW, et al. Does normal lymphocyte DNA synthesis in response to PHA exclude cell-mediated immunodepression? Clinical Immunology and Immunopathology 41: 224–229, 1986
Doria G, Adorini L, Frasca D. Immunoregulation of antibody responses in aging mice. In Goidl E, (Ed.) Aging and the immune response: cellular and humoral aspects, pp. 143–176, Dekker, New York, 1987
Endres S, Fulle H-J, Sinha B, Stoll D, Dinarello C, et al. Cyclic nucleotides differentially regulate the synthesis of tumor necrosis factor-α and interleukin-lβ by human mononuclear cells. Immunology 72, in press, 1991
Ernst D, Weigle W, McQuitty D, Rothermel A, Hobbs M. Stimulation of murine T-cell subsets with anti-CD3 antibody: age-related defects in the expression of early activation molecules. Journal of Immunology 142: 1413–1421, 1989
Ernst D, Weigle W, Thoman M. Retention of T cell reactivity to mitogens and alloantigens by Peyer’s patch cells of aged mice. Journal of Immunology 138: 26–31, 1987
Fauci AS. Mechanism of corticosteroid action on lymphocyte subpopulations II. Clinical and Experimental Immunology 71: 300–307, 1976
Fong T, Makinodan T. In situ hybridization analysis of the age-associated decline in IL-2 mRNA expressing murine T cells. Cellular Immunology 118: 199–207, 1989
Fontana A, Frei K, Bodmer S, Hofer E. Immune-mediated encephalitis: on the role of antigen-presenting cells in brain tissue. Immunological Reviews 100: 185–201, 1987
Gaylarde PM, Sarkany I. Suppression of thymidine uptake of human lymphocytes by co-trimoxazole. British Medical Journal 3: 144–146, 1972
Ghilchik MW, Morris AS, Reeves DS. Immunosuppressive powers of the antimicrobial agent trimethoprim. Nature 227: 393–394, 1970
Ghio R, Scordamaglia A, D’Elia P, et al. Inhibition of the colony forming capacity of human T lymphocytes exerted by theophylline. International Journal of Immunopharmacology 10: 299–302, 1988
Gillis S, Kozak R, Durante M, Weksler M. Immunological studies of aging: decreased production of and response to T cell growth factor by lymphocytes from aged humans. Journal of Clinical Investigation 67: 937–942, 1981
Goodwin JS, Webb DR. Regulation of the immune response by prostaglandins. Clinical Immunology and Immunopathology 15: 106–131, 1980
Gupta S. Membrane signal transduction in T cells in aging humans. Annals of the New York Academy of Sciences 568: 277–282, 1989
Hahn BH, MacDermott RP, Jacobs SB, Pletscher LS, Beale MG. Immunosuppressive effects of low doses of glucocorticoids: effect on autologous and allogenic MLRs. Journal of Immunology 124: 2812–2817, 1980
Hallgren HM, Beg N, Rodysill KJ, O’Leari JJ. Lymphocyte proliferative response to PHA and anti-CD3/Ti monoclonal antibodies. T cell surface markers expression, and serum IL-2 receptor levels as biomarker of age and health. Mechanisms of Ageing and Development 43: 175–185, 1988
Hara H, Tanaka T, Negoro S, Deguchi Y, Nishio S, et al. Age-related changes of expression of IL-2 receptor subunits and kinetics of IL-2 internalization in T cells after mitogenic stimulation. Mechanisms of Ageing and Development 45: 167–175, 1988
Hartmann G, Honikel KO, Knusel J. The specific inhibition of the DNA-directed RNA synthesis by rifamycin. Biochimica et Biophysica Acta 145: 843–844, 1967
Hauser Jr WE, Remington JS. Effect of antibiotics on the immune response. American Journal of Medicine 72: 711–716, 1982
Heine J, Adler W. The quantitative production of interferon by mitogen-stimulated mouse lymphocytes as a function of age and its effect on the lymphocytes proliferative response. Journal of Immunology 118: 1366–1369, 1977
Herberman RB, Djen JY, Kay HD, Ortaldo JR, Riccardi C, et al. Natural killer cells: characteristics and regulation of activity. Immunological Reviews 44: 43–70, 1979
Imboden JB, Stobo JD. Transmembrane signalling by the T cell antigens receptor: perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. Journal of Experimental Medicine 161: 446–452, 1985
Inamizu T, Chang M, Makinodan T. Influence of age on the production and regulation of interleukin-1 in mice. Immunology 55: 447–455, 1985
Indiveri F, Scudeletti M, Pende D, Barabino A, Russo C, et al. Inhibitory effects of a low dose of prednisone on PHA induced Ia antigen expression by human T cells and on proliferation of T cells stimulated with autologous PHA-T cells. Cellular Immunology 80: 320–327, 1983
Iwashima M, Nakayama T, Kubo M, Asano M, Tada T. Alterations in the proliferative response of T cells from aged and chimeric mice. International Archives of Allergy and Applied Immunology 83: 129–137, 1987
Janeway CA. Frontiers of the immune system. Nature 333: 804–806, 1988
Johnson JD, Hand WL, Francis JB, King-Thompson N, Corwin RW. Antibiotic uptake by alveolar macrophages. Journal of Laboratory and Clinical Medicine 95: 429–439, 1980
Kabelitz D. Do CD2 and CD3-TCR T-cell activation pathways function independently? Immunology Today 11: 44–47, 1990
Kay AB. Modulation of eosinophil function in vitro. Clinical and Experimental Allergy 20 (Suppl. 4): 31–34, 1990
Lightart GJ, Van Vlokhoven PC, Schuit HRE, Haaijman JJ. SENIEUR protocol. Mechanisms of Ageing and Development 28: 47–55, 1984
Mandell GL. Interaction of intraleukocytic bacteria and antibiotics. Journal of Clinical Investigation 52: 1673–1679, 1973
Meuer SC, Hussey RE, Cantrell DA, Hodgdon JC, Schlossman SF, et al. Triggering of the T3-Ti antigen receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proceedings of the National Academy of the Sciences USA 81: 1509–1515, 1984a
Meuer SC, Hussey RE, Fabbi M, Fox D, Acuto O, et al. An alternative pathway of T cell activation: a functional role for the 50 KD T11 sheep erythrocyte receptor protein. Cell 36: 897–902, 1984b
Meuer SC, Roux MM, Schraven B. The alternative pathway of T cell activation; biology, pathophysiology and perspectives for immunopharmacology. Clinical Immunology and Immunopathology 50: 5133–5139, 1989
Miller R. Age-associated decline in precursor frequency for different T cell-mediated reactions, with preservation of helper or cytotoxic effect per precursor cell. Journal of Immunology 132: 63–68, 1984
Miller R, Jacobson F, Weil G, Simons E. Diminished calcium influx in lectin-stimulated T cell from old mice. Journal of Cellular Physiology 132: 337–342, 1987
Miller R, Stutman O. Decline, in aging mice, of the anti-2, 4, 6-trinitrophenyl (TNP) cytotoxic T cell response attributable to less of LYt-2-, interleukin 2-producing helper cell function. European Journal of Immunology 11: 751–756, 1981
Moretta A, Pantaleo G, Moretta L, Cerottini JC, Mingari MC. Direct demonstration of the clonogenic potential for every human peripheral blood T cell: clonal analysis of HLA-Dr expression and cytolytic activity. Journal of Experimental Medicine 157: 743–748, 1983
Moretta A, Poggi A, Olive D, et al. Selection and characterization of T cell variants lacking molecules involved in T cell activation (T3, T cell receptor, T44 and T11): analysis of the functional relationship among different pathways of activation. Proceedings of the National Academy of the Sciences USA 84: 1654–1658, 1987
Morgano A, Pierri I, Stagnaro R, Setti M, Puppo F, et al. Decreased lymphocyte blastogenesis, IL-2 production and NK activity following nifedipine administration to healthy humans. European Journal of Clinical Pharmacology 39: 545–551, 1990
Munoz J, Geister R. Inhibition of phagocytosis by aureomycin. Proceedings of the Society for Experimental Biology and Medicine 75: 367–370, 1950
Nagel J, Chopra R, Chrest F, McCoy M, Schneider E, et al. Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompaned by decreased mRNA expression in phytohemoagglutinin-stimulated cells from elderly donors. Journal of Clinical Investigation 81: 1096–1102, 1988
Nel AE, Dirienzo W, Stefanini GF, Wooten MW, Canonica GW, et al. Inhibition of T3-mediated T-cell proliferation by Ca2+/channel blockers and inhibitors of Ca2+/phospholipid-dependent kinase. Scandinavian Journal of Immunology 24: 283–291, 1986
Paegelow I, Werner H. Influence of adrenergic agonist and antagonist on lymphokine secretion in vitro. International Journal of Immunopharmacology 9: 761–768, 1987
Pierri I, Rogna S, Stagnaro R, Piovano PL, Morgano A, et al. Comparison between famotidine and ranitidine immunomodulatory effects in man. International Journal of Immunotherapy 4: 243–248, 1988
Poggi A, Bottino C, Zocchi M, Pantaleo G, Mingari C, et al. CD3+W31− peripheral lymphocytes lack T44 (CD28), a surface molecule involved in activation of T cells bearing the α-β heterodymer. European Journal of Immunology 17: 1065–1068, 1987
Poggi A, Sciallero S, Indiveri F. In vitro effects of ranitidine on human lymphocyte function. International Journal of Immunopharmacology 7: 369–A, 1985
Proust J, Filburn C, Harrison S, Buchholz M, Nordin A. Age-related defect in signal transduction during lectin activation of murine T lymphocytes. Journal of Immunology 139: 1472–1478, 1987
Ricci M, Del Prete GF, Maggi E, Romagnani S. New trends on the pathogenic aspect of allergic bronchial asthma. Respiration 50 (Suppl. 2): 103–115, 1986
Rytel M, Larratt K, Turner P, Kalbfleisch J. Interferon response to mitogens and viral antigens in elderly and young adult subjects. Journal of Infectious Diseases 153: 984–987, 1986
Scordamaglia A, Ciprandi G, Mirabelli S, Aquilina R, Calcagno L, et al. Bacampicillin and the immune response. Journal of Antimicrobial Chemotherapy 19: 791–793, 1987
Scordamaglia A, Ciprandi G, Ruffoni S, Caria M, Paolieri F, et al. Theophylline and immune system: in vitro and in vivo effects. Clinical Immunology and Immunopathology 48: 238–246, 1988a
Scordamaglia A, Cipro G, Pizzorno G, Ruffoni S, Colombo F, et al. Tetroxoprim and sulphadiazine do not affect the immune response. Medical Science Research 16: 1209–1210, 1988b
Scudeletti M, Ciprandi G, Pronzato C, Passalacqua G, Imbimbo B, et al. Comparison of the immunomodulation of prednisone, dexamethasone and deflazacort on T-cell activation pathways and gamma-interferon production. International Journal of Immunotherapy 2: 85–90, 1989
Scudeletti M, Pende D, Barabino A, Imbimbo B, Grifoni V, et al. Effect of single oral doses of prednisone and deflazacort on human lymphocyte distribution and functions: analysis with monoclonal antibodies. In Avioli LV, et al. (Eds) Glucocorticoid effects, pp. 335–344, Plenum, New York, 1984
Scudeletti M, Piccardo C, Piovano P, Imbimbo B, Indiveri F. Effects of a new heterocyclic glucocorticoid, deflazacort (DFC), on the functions of lymphocytes from patients with rheumatoid arthritis (RA). International Journal of Immunopharmacology 9: 133–139, 1987
Simonsen M. May T3 protect us at all? Immunology Today 5: 314–319, 1984
Sollid LM, Kvale D, Brandtzaeg P, Markussen G, Thorby E. Interferon-gamma enhances expression of secretory component, the epithelial receptor for polymeric immunoglobulins. Journal of Immunology 138: 4303–4306, 1987
Souillet G, Rousset F, de Vries JE. Alpha-interferon treatment of patients with hyper IgE syndrome. Correspondence. Lancet 1: 1384, 1989
Stevenson MC, Fauci AS. Effects of corticosteroids on the function and distribution of human lymphocytes. In Franklin EG (Ed.) Clinical immunology update, pp. 337–355, Churchill-Livingstone, Edinburgh, 1981
Thoman M, Weigle W. Lymphokines and aging: interleukin-2 production and activity in aged animals. Journal of Immunology 127: 2102–2106, 1981
Thoman M, Weigle W. Partial restoration of Con-A-induced proliferation, IL-2 receptor expression, and IL-2 synthesis in aged murine lymphocytes by phorbol myristate acetate and ionomycin. Cellular Immunology 114: 1–11, 1988
Thoman M, Weigle W. The cellular and subcellular bases of immunosenescence. Advances in Immunology 46: 201–253, 1989
Tosi O, Kraft R, Luzi P, Cintorino M, Frankhauser G, et al. Involution pattern of the human thymus. I. Size of the cortical area as a function of age. Clinical and Experimental Immunology 47: 497–504, 1982
Wade A, Szewcuk M. Aging, idiotype repertoire shifts, and compartmentalization of the mucosal-associated lymphoid system. Advances in Immunology 36: 143–188, 1984
Wade A, Szewcuk M. Aging and compartmentalization of the mucosa immune system. Advances in Experimental Medicine and Biology 216B: 1383–1393, 1987
Weiss A, Imboden JB, Schoback D, Stobo JD. Role of T3 surface molecules in human T-cell activation: T3-dependent activation results in an increase in cytoplasmic free calcium. Proceedings of the National Academy of the Sciences USA 81: 169–174, 1984a
Weiss A, Wiskocil RL, Stobo JD. The role of T3 surface molecules in the activation of human T cells: a two-stimulus requirement for IL-2 production reflects events occurring at a pre-translational level. Journal of Immunology 133: 123–127, 1984b
Weksler M. The thymus gland and aging. Annals of Internal Medicine 98: 105–107, 1983
Weksler ME, Hutteroth TH. Impaired lymphocyte function in aged humans. Journal of Clinical Investigation 53: 99–104, 1974
Whisler RL, Newhouse YG. Function of T cells from elderly humans: reductions of membrane events and proliferative responses mediated via T3 determinants and diminished elaboration of soluble T-cell factors for B-cell growth. Cellular Immunology 99: 422–433, 1986
Whisler RL, Newhouse YG, Ennist D, Lachman LB. Human B-lymphocyte colony responses: suboptimal colony responsiveness in aged humans associated with defective function of T cells and monocytes. Cellular Immunology 94: 133–146, 1985
Winchurch R, Togo J, Adler W. Supplemental zinc (Zn2+) restores antibody formation in cultures of aged spleen cells. II. Effects on mediator production. European Journal of Immunology 17: 127–132, 1987
Wu W, Pahlavani M, Cheung H, Richardson A. The effect of aging on the expression of interleukin 2 messenger ribonucleic acid. Cellular Immunology 100: 224–231, 1986
Yokota T, Arai N, de Vries J, Spits H, Banchereau J, et al. Molecular biology of IL-4 and IL-5 genes and biology of their products that stimulate T cells, T cells and hemopoietic cells. Immunology Review 102: 137–187, 1988
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Scordamaglia, A., Ciprandi, G., Indiveri, F. et al. The Effect of Aging on Host Defences. Drugs & Aging 1, 303–316 (1991). https://doi.org/10.2165/00002512-199101040-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002512-199101040-00006