Serum cytokine profiles in healthy young and elderly population assessed using multiplexed bead-based immunoassays

Hyun Ok Kim, Han-Soo Kim, Jong-Chan Youn, Eui-Cheol Shin, Sungha Park, Hyun Ok Kim, Han-Soo Kim, Jong-Chan Youn, Eui-Cheol Shin, Sungha Park

Abstract

Background: Lipid metabolites and cytokines, including chemokines and growth factors, are the key regulators of immune cell function and differentiation, and thus, dysregulation of these regulators is associated with various human diseases. However, previous studies demonstrating a positive correlation of cytokine levels with aging may have been influenced by various environmental factors and underlying diseases. Also, data regarding cytokine profiling in the elderly are limited to a small subset of cytokines.

Methods: We compared the profiles of 22 cytokines, including chemokines and growth factors, in a case-controlled study group of a gender-matched, healthy cohort of 55 patients over the age of 65 and 55 patients under the age of 45. Assessment of serum cytokine concentrations was performed using commercially-available multiplex bead-based sandwich immunoassays.

Results: Soluble CD40 ligand (sCD40L) and transforming growth factor alpha (TGF-α) levels were significantly higher in the elderly patients, whereas granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly lower in the elderly patients. The partial correlation analysis demonstrating the correlation between cytokine levels when controlled for gender, systolic blood pressure, total cholesterol, HDL cholesterol, triglyceride, and serum creatinine levels further demonstrated that G-CSF, GM-CSF, and MCP-1 had significant negative correlations with age, whereas sCD40L and TGF-α had significant positive correlations.

Conclusions: Future studies will focus on examining the significance of these age-related changes in circulating cytokines and other biological markers and their potential contribution to the development of different age-associated diseases.

Figures

Figure 1
Figure 1
Simple correlation between age and serum biomarkers (sCD40L, G-CSF, GM-CSF, and TGF-α in pg/mL). The × axis is age. The Y axis consists of log transformed sCD40L, G-CSF, GM-CSF and TGF-α. Simple correlation analysis was performed between age and the cytokines. Age showed significant positive correlation with log transformed sCD40L (R = 0.257, P = 0.007) and log transformed TGF-α (R = 0.232, P = 0.015), whereas age showed significant negative correlation with log transformed G-CSF (R = -0.232, P = 0.016) and log transformed GM-CSF (R = -0.249, P = 0.009).

References

    1. Franceschi C, Capri M, Monti D, Caruso C, Candore G, Vasto S, Oliveri F, Marchegiani F, Sansoni P, Baggio G, Mari D, Passarino G, De Benedictis G. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev. 2007;128:92–105. doi: 10.1016/j.mad.2006.11.016.
    1. Park S, Kim HO, Kim HS. Aging associated decline in immunity and therapeutic strategies to counteract it. Tissue Engin Regen Med. 2011;8:124–132.
    1. Trzonkowski P, Szmit E, Mysliwska J, Mysliwski A. CD4+CD25+ T-regulatory cells inhibit cytotoxic activity of CTL and NK- cells in humans-impact of immunosenescence. Clin Immunol. 2006;119:307–316. doi: 10.1016/j.clim.2006.02.002.
    1. Dejaco C, Duftner C, Schirmer M. Are regulatory T cells linked with aging? Exp Gerontol. 2006;41:339–345. doi: 10.1016/j.exger.2006.01.008.
    1. Zanni F, Vescovini R, Biasini C, Fagnoni F, Zanlari L, Telera A, De Pede P, Passeri G, Pedrazzoni M, Passeri M, Franceschi C, Sansoni P. Marked increase with age of type 1 cytokines within memory and effector/cytotoxic CD8+ T cells in humans: a contribution to the relationship between inflammation and immunosenescence. Exp Gerontol. 2003;38:981–987. doi: 10.1016/S0531-5565(03)00160-8.
    1. Wick G, Grubeck-Loebenstein B. Primary and secondary alterations of immune reactivity in the elderly: impact of dietary factors and diseas. Immunol Rev. 1997;160:171–184. doi: 10.1111/j.1600-065X.1997.tb01037.x.
    1. Roubenolf R, Harris TB, Abad LW, Wilson PW, Dallal GE, Dinarello CA. Monocyte cytokine production in an elderly population: effect of age and inflammation. J Gerontol A Biol Sci Med Sci. 1998;53:M20–M26.
    1. Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Guralnik JM, Long DL. The origin of age-related proinflammatory state. Blood. 2005;105:2294–2299. doi: 10.1182/blood-2004-07-2599.
    1. Krabbe KS, Bruunsgaard H, Hansen CM, Moller K, Fonsmark L, Qvist J, Madsen PL, Kronborg G, Andersen HO, Skinhoj P, Pedersen BK. Ageing is associated with a prolonged fever response in human endotoxemia. Clin Diagn Lab Immunol. 2001;8:333–338.
    1. Woodward M, Rumley A, Lowe GD, Tunstall-Pedoe H. C-reactive protein: associations with haematological variables, cardiovascular risk factors and prevalent cardiovascular disease. Br J Haematol. 2003;122:135–141. doi: 10.1046/j.1365-2141.2003.04387.x.
    1. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.
    1. Beharka AA, Meydani M, Wu D, Leka LS, Meydani A, Meydani SN. Interleukin-6 production does not increase with age. J Gerontol A Biol Sci Med Sci. 2001;56A:B81–B88.
    1. Ahluwalia N, Mastro AM, Ball R, Miles MP, Rajendra R, Handte G. Cytokine production by stimuated mononuclear cells did not change with aging in apparently healthy, well-nourished women. Mech Ageing Rev. 2001;122:1269–1279. doi: 10.1016/S0047-6374(01)00266-4.
    1. Baggio G, Donazzan S, Monti S, Mari D, Martini S, Gabelli C, Dalla Vestra M, Previato L, Guido M, Pigozzo S, Cortella I, Crepaldi G, Franceschi C. Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of vascular risk factors. FASEB J. 1998;12:433–437.
    1. Goetzl EJ, Huang MC, Kon J, Patel K, Schwartz JB, Fast K, Ferrucci L, Madara K, Taub DD, Long DL. Gender specificity of altered human immune cytokine profile in aging. FASEB J. 2010;24:3580–3589. doi: 10.1096/fj.10-160911.
    1. Zhu S, Patel KV, Bandinelli S, Ferrucci, Guralnik JM. Predictors of interleukin-6 elevation in older adults. J Am Geriatr Soc. 2009;57:1672–1677. doi: 10.1111/j.1532-5415.2009.02426.x.
    1. Antoniades C, Bakogiannis C, Tousoulis D, Antonopoulos AS, Stefanadis C. The CD40/CD40 Ligand system: Linking inflammation with atherothrombosis. J Am Coll Cardiol. 2009;54:669–677. doi: 10.1016/j.jacc.2009.03.076.
    1. Shonbeck U, Libby P. CD40 signaling and plaque instability. Circ Res. 2001;89:1092–1103. doi: 10.1161/hh2401.101272.
    1. Chen C, Chai H, Wang X, Jiang J, Jamaluddin MS, Liao D, Zhang Y, Wang H, Bharadwaj U, Zhang S, Li M, Lin P, Yao Q. Soluble CD40 ligand induces endothelial dysfunction in human and porcine coronary artery endothelial cells. Blood. 2008;112:3205–3216. doi: 10.1182/blood-2008-03-143479.
    1. Derynck R. Transforming growth factor alpha. Cell. 1998;54:593–595.
    1. Pike LJ, Marquardt H, Todaro GJ, Gallis B, Casnellie JE, Bornestein P, Krebs EG. Transforming growth factor and epidermal growth factor stimulate the phosphorylation of a synthetic, tyrosine-containing peptide in a similar manner. J Biol Chem. 1982;257:14628–14631.
    1. Booth BW, Smith GH. Roles of transforming growth factor-alpha in mammary development and disease. Growth Factors. 2007;25:227–235. doi: 10.1080/08977190701750698.
    1. McClain DA, Paterson AJ, Roos MD, Wei X, Kudlow JE. Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells. Proc Natl Acad Sci USA. 1992;89:8150–8154. doi: 10.1073/pnas.89.17.8150.
    1. Buzzeo MP, Yang J, Casella G, Reddy V. Hematopoietic stem cell mobilization with G-CSF induces innate inflammation yet suppresses adaptive immune gene expression as revealed by microarray analysis. Exp Hematol. 2007;35:1456–1465. doi: 10.1016/j.exphem.2007.06.001.
    1. Baldridge MT, King KY, Goodell MA. Inflammatory signals regulate hematopoietic stem cells. Trends Immunol. 2011;32:57–65. doi: 10.1016/j.it.2010.12.003.
    1. Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nature Immunol. 2006;7:311–317.
    1. Tsou CL, Peters W, Si Y, Slaymaker S, Aslanian AM, Weisberg SP, Mack M, Charo IF. Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest. 2007;17:902–909.
    1. de Lemos JA, Morrow DA, Sabatine MS, Murphy SA, Gibson CM, Antman. Association between plasma levels of monocyte mhemoattractant protein-1 and long-term clinical outcomes in patients with acute coronary syndromes. Circulation. 2003;107:690–695. doi: 10.1161/01.CIR.0000049742.68848.99.
    1. Inadera H, Egashira K, Takemoto M, Ouchi Y, Matsushima K. Increase in circulating levels of monocyte chemoattractant protein-1 with aging. J Interferon Cytokine Res. 1999;19:1179–1182. doi: 10.1089/107999099313127.
    1. Gerli R, Monti D, Bistoni O, Mazzone AM, Peri G, Cossarizza A, Di Gioacchino M, Cesarotti ME, Doni A, Mantovani A, Franceschi C, Paganelli R. Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev. 2000;121:37–46.
    1. de Martinis M, Modesti M, Ginaldi L. Phenotypic and functional changes of circulating monocytes and polymorphonuclear leucocytes from elderly persons. Immunol Cell Biol. 2004;82:415–420. doi: 10.1111/j.0818-9641.2004.01242.x.

Source: PubMed

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