Cytokine production pathway in the elderly
It is well known that aging is associated with various alterations in lymphoid cell functions, particularly with a progressive decline in immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena. Many studies have been focused on the mechanisms of the immunologic features of aging. This review describes our results of studies performed to determine the influence of age on the capacity to produce interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6) and tumor necrosis factor (TNF). Mitogen-stimulated cultures of mononuclear cells (MNC) from human beings were assessed for cytokine-producing capacity. A significant decrease in IFN-γ and IL-2 production by MNC cultures from elderly individuals was observed. No significant difference was instead observed between cultures from elderly individuals and those from young ones as regards TNF-α, IL-4 and IL-6 production. Mitogen or antigen-stimulated cultures of MNC from aged mice also displayed a significant decrease in IFN-γ and IL-2 production as well as TNF-β. Instead IL-4 and IL-5 production significantly increased in these cultures. We suggest that this imbalanced cytokine production may well account for the pattern of immune response which may be observed in the elderly, i.e. a normal or increased humoral response (including autoimmune responses) in face of a low T cell immune responsiveness.
Key WordsAging Autoimmunity Cytokines Immune response Immunodeficiency
Unable to display preview. Download preview PDF.
- 11.Paul WE, Ohara J: B-cell stimulatory factor-1/interleukin 4. Ann Rev Immunol 1987;5:429–459.Google Scholar
- 12.Koike M, Takatsu K: IL-5 and its receptor: Which role do they play in the immune response? Int Arch Allergy Appl Immunol 1994;104:1–9.Google Scholar
- 17.Nagel JE, Chopra RK, Chrest FJ, McCoy MT, Schneider EL, Holbrook NJ, Adler WH: Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors. J Clin Invest 1988; 81:1096–1102.PubMedCrossRefGoogle Scholar
- 19.Chopra RK, Holbrook NJ, Powers DC, McCoy MT, Adler WH, Nagel JE: Interleukin 2, interleukin 2 receptor, and interferon-gamma synthesis and mRNA expression in phorbol myristate acetate and calcium ionophore A23187-stimulated T cells from elderly humans. Clin Immunol Immunopathol 1989;53:297–308.PubMedCrossRefGoogle Scholar
- 22.Caruso C, Di Lorenzo G, Cigna D, Ingrassia A, Colucci AT, Modica MA, Candore G: Cytokine production pathway in elderly subjects. EOS 1992;12:210–212.Google Scholar
- 27.Lio D, D'Anna C, Gervasi F, Cigna D, Modica MA, Candore G, Caruso C: In vitro impairment of interleukin-5 production in HLA-B8, DR3-positive individuals. Implications for immunoglobulin A synthesis dysfunction. Hum Immuno. in press.Google Scholar
- 28.Chen WF, Liu SL, Gao XM, Pang XM: The capacity of lymphokine production by peripheral blood lymphocytes from aged humans. Immunol Invest 1987;15:575–583.Google Scholar
- 32.Daynes RA, Araneo BA, Ershler WB: Altered regulation of IL-6 production with normal aging. J Immunol 1993;50:5219–5230.Google Scholar
- 41.Caruso C, Modica MA, Candore G, Di Lorenzo G, Durante M, Di Giulio C: In vivo thymopentin modulation of mitogen-responsive T-cell precursor frequency. Int J Immunother 1989;5:133–137.Google Scholar
- 43.Caruso C, Di Lorenzo G, Ingrassia A, Colucci AT, Di Giulio C, Candore G: Decline in mitogen responsive T cell precursor frequency with advancing age. EOS 1992;2:8–10.Google Scholar
- 44.Caruso C, Candore G, Cigna D, Lio D, Lucania G, Modica MA, Melluso M, Mansueto P, Di Lorenzo G: Espressione dei marker di attivazione dei T linfociti degli anziani dopo stimolazione in vitro con mitogeni Atti XIV Congr Soc It Immunol Immunopat, 1995, 473–477.Google Scholar