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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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.
Antonelli A, Rotondi M, Fallahi P et al (2006) Increase of CXC chemokine CXCL10 and CC chemokine CCL2 serum levels in normal ageing. Cytokine 34:32–38PubMedCrossRefGoogle Scholar
Cazzola M, Polosa R (2006) Anti-TNFα and Th1 cytokine-directed therapies for the treatment of asthma. Curr Opin Allergy Clin Immunol 6:43–50PubMedCrossRefGoogle Scholar
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 44:1812–1818PubMedCrossRefGoogle Scholar
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 68:340–347PubMedGoogle Scholar
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)Google Scholar
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. 133–157Google Scholar
Mariani E, Roda P, Mariani AR et al (1990) Age-associated changes in CD8+ and CD16+ cell reactivity: clonal analysis. Clin Exp Immunol 81:479–484PubMedCrossRefGoogle Scholar
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 90:10193–10197PubMedCrossRefGoogle Scholar
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 27:159–163CrossRefPubMedGoogle Scholar
Maurer M, von Stebut E (2004) Molecules in focus. Macrophage inflammatory protein-1. Int J Biochem Cell Biol 36:1882–1886PubMedCrossRefGoogle Scholar
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 43:983–998PubMedCrossRefGoogle Scholar
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 37:309–314PubMedCrossRefGoogle Scholar
Ono JS, Nakamura T, Miyazaki D et al (2003) Chemokines: roles in leukocyte development, trafficking and effector function. J Allergy Clin Immunol 111:1185–1199PubMedCrossRefGoogle Scholar
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 26:2030–2034Google Scholar
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 37:257–263PubMedCrossRefGoogle Scholar
Pawelec G, Solana R, Remarque E et al (1998) Impact of aging on innate immunity. J Leukoc Biol 64:703–712PubMedGoogle Scholar
Pawelec G, Barnett Y, Forsey R et al (2002) T cells and ageing, January 2002 update. Front Biosci 7:d1056–d1183PubMedGoogle Scholar
Plowden J, Renshaw-Hoelscher M, Engleman C et al (2004) Innate immunity in ageing: impact on macrophage function. Aging Cell 3:161–167PubMedCrossRefGoogle Scholar
Podkowka R, Wisniewska J, Korybalska K et al (2002) Plasma level of interleukin-6 and interleukin-8 in the elderly. Przegl Lek 59:230–233PubMedGoogle Scholar
Pulsatelli L, Meliconi R, Mazzetti I et al (2000) Chemokine production by peripheral blood mononuclear cells in elderly subjects. Mech Ageing Dev 121:89–100PubMedCrossRefGoogle Scholar
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 71:590–598PubMedGoogle Scholar