Abstract
Cellular components of both adaptive and innate immune systems produce different chemokines and cytokines, involved in different signalling pathways among cells, and modulate effector function during immune response, playing a key role in the regulation of the type and extent of the immune response in the elderly. We evaluated the circulating concentration of selected chemokines: MCP-1, MIP-1α, IL-8, RANTES together with IL-6 and TNF-α in plasma obtained from a group of healthy old subjects, in order to highlight possible differences in the synthesis of these factors, assuming that both the cytokine and the chemokine networks are remodelled with ageing. The simultaneous evaluation was performed by a multiplex analysis system. In addition, since micronutrient deficiency may underlie an inflammatory response, the association between chemokine levels and a nutritional element such as zinc was also evaluated, since the immune system is the first system to be affected by changing zinc levels, due to its high cell turnover. A progressive age-related increase of plasma concentrations of all soluble factors was observed. The increment was particularly evident for IL-6, IL-8, MCP-1 and TNF-α in the over 85-year-old group in concomitance with increasing percentages of subjects with low circulating levels of zinc. In conclusion, the remodelling of chemokine profiles, skewed to Th2 response by both advanced ages and circulating levels of zinc, might reflect different states of activation and/or responsiveness of the human immune cell/mediator network, thus influencing the ability to develop rapid innate and long-lasting adaptive immune responses with advancing age.
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Antonelli A, Rotondi M, Fallahi P et al (2006) Increase of CXC chemokine CXCL10 and CC chemokine CCL2 serum levels in normal ageing. Cytokine 34:32–38
Baggiolini M (1998) Chemokines and leukocyte traffic. Nature 392:565–568
Brod SA (2000) Unregulated inflammation shortens human functional longevity. Inflamm Res 49:561–570
Cazzola M, Polosa R (2006) Anti-TNFα and Th1 cytokine-directed therapies for the treatment of asthma. Curr Opin Allergy Clin Immunol 6:43–50
Deo R, Khera A, McGuire DK et al (2004) Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors and subclinical atherosclerosis. J Am Coll Cardiol 44:1812–1818
Facchini A, Mariani E, Mariani AR et al (1987) Increased number of circulating Leu 11+ (CD 16) large granular lymphocytes and decreased NK activity during human ageing. Clin Exp Immunol 68:340–347
Fraker PJ, King LE (2004) Reprogramming of the immune system during zinc deficiency. Annu Rev Nutr 24:277–298
Gabriel P, Cakman I, Rink L (2002) Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly. Exp Gerontol 37:235–247
Gerli R, Monti D, Bistoni O et al (2000) Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev 121:37–46
Gu L, Tseng S, Horner RM et al (2000) Control of Th2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404:407–411
Hambidge M (2000) Human zinc deficient. J Nutr 130:1344S–1349S
Ibs KH, Rink L (2003) Zinc-altered immune function. J Nutr 133:1452S–1456S
Inadera H, Egashira K, Takemoto M et al (1999) Increase in circulating levels of monocyte chemoattractant protein-1 with aging. J Interferon Cytokine Res 19:1179–1182
Licastro F, Candore G, Lio D et al (2005) Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing 2:1–14
Ligthart GJ, Corberand JX, Fournier C et al (1984) Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev 28:47–55
Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5:133–139
Malavolta M, Costarelli L, Giacconi R, Muti E, Bernardini G, Tesei S, Cipriano C, Mocchegiani E (2006) Single and three-colours flow cytometry assay for intracellular zinc ion availability in human lymphocytes with Zinpyr-1 and double immunofluorescence: relationship with metallothioneins. Cytometry A (in press)
Mariani E, Facchini A (2003) Characterisation of NK cells in the elderly. In: Pawelec G (ed) Advances in cell ageing and gerontology series, vol. 13. Basic biology and clinical impact of immunosenescence. Elsevier BV, Amsterdam, pp. 133–157
Mariani E, Roda P, Mariani AR et al (1990) Age-associated changes in CD8+ and CD16+ cell reactivity: clonal analysis. Clin Exp Immunol 81:479–484
Matsusaka T, Fujikawa K, Nishio Y et al (1993) Transcription factors NK-IL6 and NK-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc Natl Acad Sci USA 90:10193–10197
Maugeri D, Russo MS, Franze C et al (1998) Correlations between C-reactive protein, interleukin-6, tumor necrosis factor-alpha and body mass index during senile osteoporosis. Arch Gerontol Geriatr 27:159–163
Maurer M, von Stebut E (2004) Molecules in focus. Macrophage inflammatory protein-1. Int J Biochem Cell Biol 36:1882–1886
Menten P, Wuyts A, Van Damme J (2002) Macrophage inflammatory protein-1. Cytokine Growth Factor Rev 13:455–481
Moser B, Williman K (2004) Chemokines: role in inflammation and immune surveillance. Ann Rheum Dis 63:ii84–ii89
Niemir ZI, Stein H, Ciechanowicz A (2004) The in situ expression of interleukin-8 in the normal human kidney and in different morphological forms of glomerulonephritis. Am J Kidney Dis 43:983–998
Olivieri F, Bonafè M, Cavallone L et al (2002) The-174 C/G locus affects in vitro/in vivo IL-6 production during aging. Exp Gerontol 37:309–314
Ono JS, Nakamura T, Miyazaki D et al (2003) Chemokines: roles in leukocyte development, trafficking and effector function. J Allergy Clin Immunol 111:1185–1199
Paganelli R, Scala E, Rosso R et al (1996) A shift to Th0 cytokine production by CD4+ cells in human longevity: studies on two healthy centenarians. J Immunol 26:2030–2034
Paganelli R, Di Iorio A, Patricelli L et al (2002) Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild–moderate Alzheimer’s disease patients. Exp Gerontol 37:257–263
Pawelec G, Solana R, Remarque E et al (1998) Impact of aging on innate immunity. J Leukoc Biol 64:703–712
Pawelec G, Barnett Y, Forsey R et al (2002) T cells and ageing, January 2002 update. Front Biosci 7:d1056–d1183
Plowden J, Renshaw-Hoelscher M, Engleman C et al (2004) Innate immunity in ageing: impact on macrophage function. Aging Cell 3:161–167
Podkowka R, Wisniewska J, Korybalska K et al (2002) Plasma level of interleukin-6 and interleukin-8 in the elderly. Przegl Lek 59:230–233
Prasad AS (2000) Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis 182:S62–S68
Pulsatelli L, Meliconi R, Mazzetti I et al (2000) Chemokine production by peripheral blood mononuclear cells in elderly subjects. Mech Ageing Dev 121:89–100
Ravaglia G, Forti P, Maioli F et al (2000) Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged ≥90 y1–3. Am J Clin Nutr 71:590–598
Rink L, Gabriel P (2000) Zinc and the immune system. Proc Nutr Soc 59:541–552
Sanjiv AL, Cyster JG (2001) Chemokines as regulators of T cell differentiation. Nat Immunol 2:102–107
Sarkar D, Fisher PB (2006) Molecular mechanisms of aging-associated inflammation. Cancer Lett 236:13–23
Shankar AH, Prasad AS (1998) Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 68:447S–463S
Solana R, Mariani E (2000) NK and NK/T cells in human senescence. Vaccine 18:1613–1620
Stellwagen D, Malenka RC (2006) Synaptic scaling mediated by glial TNF-alpha. Nature 440:1054–1059
Tieri P, Valensin S, Latora V et al (2005) Quantifying the relevance of different mediators in the human immune cell network. Bioinformatics 21:1639–1643
Wieczorowska-Tobis K, Niemir ZI, Podkowka R et al (2006) Can an increased level of circulating IL-8 be a predictor of human longevity? Med Sci Monit 12:CR118–CR121
Wong MM, Fish EN (2003) Chemokines: attractive mediators of the immune response. Semin Immunol 15:5–14
World Health Organization (1996) Zinc. In: trace elements in human nutrition and health. WHO, Geneve, pp. 72-104
Acknowledgements
This work was partially supported by grants from Bologna University (60% fund), Ricerca Corrente IOR, Italian Health Ministry fund, and was performed under the aegis of the EU ZINCAGE project (FOOD-CT-2003-506850). The authors thank Mrs Patrizia Rappini and Graziella Salmi for typing assistance.
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Presented at the ZincAge Conference, Madrid, February 10–13, 2006.
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Mariani, E., Cattini, L., Neri, S. et al. Simultaneous evaluation of circulating chemokine and cytokine profiles in elderly subjects by multiplex technology: relationship with zinc status. Biogerontology 7, 449–459 (2006). https://doi.org/10.1007/s10522-006-9060-8
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DOI: https://doi.org/10.1007/s10522-006-9060-8