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Relationship between vitamin D and inflammatory markers in older individuals

Abstract

In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP) ≥ 10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1β, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1—adjusted for age, sex, and parathyroid hormone (PTH); model 2—including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) (β ± SE = −0.11 ± 0.03, p = <0.0001) and log (hsCRP) (β ± SE = −0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (β ± SE = −0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) (β ± SE = −0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals.

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References

  1. Amer M, Qayyum R (2012) Relation between serum 25-hydroxyvitamin D and C-reactive protein in asymptomatic adults (from the continuous National Health and Nutrition Examination Survey 2001 to 2006). Am J Cardiol 109:226–230

  2. Autier P, Boniol M, Pizot C, Mullie P (2014) Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2:76–89

  3. Börgermann J, Lazouski K, Kuhn J, Dreier J, Schmidt M, Gilis-Januszewski T, Knabbe C, Gummert JF, Zittermann A (2012) 1,25-Dihydroxyvitamin D fluctuations in cardiac surgery are related to age and clinical outcome. Crit Care Med 40:2073–2081

  4. Clendenen TV, Koenig KL, Arslan AA et al (2011) Factors associated with inflammation markers, a cross-sectional analysis. Cytokine 56:769–778

  5. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W (2008) Independent association of low serum 25-hydroxyvitamin and 1,25-dihydroxyvitamin D levels with all cause and cardiovascular mortality. Arch Intern Med 168:1340–1349

  6. Equils O, Naiki Y, Shapiro AM, Michelsen K, Lu D, Adams J, Jordan S (2006) 1,25-dihydroxyvitamin D inhibits lipopolysaccharide-induced immune activation in human endothelial cells. Clin Exp Immunol 143:58–64

  7. Fava GA (1983) Assessing depressive symptoms across cultures: Italian validation of the CES-D self-rating scale. J Clin Psychol 39:249–251

  8. Ferrucci L, Bandinelli S, Benvenuti E, Di Iorio A, Macchi C, Harris TB, Guralnik JM (2000) Subsystems contributing to the decline in ability to walk: bridging the gap between epidemiology and geriatric practice in the InCHIANTI study. J Am Geriatr Soc 48:1618–1625

  9. Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Guralnik JM (2005) The origins of age-related proinflammatory state. Blood 105:2294–2299

  10. Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254

  11. Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448–454

  12. Gabay C, Smith MF, Eidlen D, Arend WP (1997) Interleukin 1 receptor antagonist (IL-1 Ra) is an acute-phase protein. J Clin Invest 99:2930–2940

  13. Gannagé-Yared MH, Azoury M, Mansour I, Baddoura R, Halaby G, Naaman R (2003) Effects of a short-term calcium and vitamin D treatment on serum cytokines, bone markers, insulin and lipid concentrations in healthy post-menopausal women. J Endocrinol Invest 26:748–753

  14. Gray A, McMillan DC, Wilson C, Williamson C, O’Reilly DS, Talwar D (2005) The relationship between the acute changes in the systemic inflammatory response, lipid soluble antioxidant vitamins and lipid peroxidation following elective knee arthroplasty. Clin Nutr 24:746–750

  15. Helming L, Böse J, Ehrchen J, Schiebe S, Frahm T, Geffers R, Probst-Kepper M, Balling R, Lengeling A (2005) 1alpha,25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation. Blood 106:4351–4358

  16. Hewison M (2010) Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin N Am 39:365–379

  17. Hilger J, Friedel A, Herr R, Rausch T, Roos F, Wahl DA, Pierroz DD, Weber P, Hoffmann K (2014) A systematic review of vitamin D status in populations worldwide. Br J Nutr 111:23–45

  18. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

  19. Il’yasova D, Colbert LH, Harris TB, Newman AB, Bauer DC, Satterfield S, Kritchevsky SB (2005) Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomarkers Prev 14:2413–2418

  20. Jablonski KL, Chonchol M, Pierce GL, Walker AE, Seals DR (2011) 25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults. Hypertension 57:63–69

  21. Kaaks R, Riboli E (1997) Validation and calibration of dietary intake measurements in the EPIC project: methodological considerations. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol 26:S15–S25

  22. Katz S, Akpom CA (1976) A measure of primary sociobiological functions. Int J Health Serv 6:493–508

  23. Laird E, McNulty H, Ward M, Hoey L, McSorley E, Wallace JM, Carson E, Molloy AM, Healy M, Casey MC, Cunningham C, Strain JJ (2014) Vitamin D deficiency is associated with inflammation in Older irish adults. J Clin Endocrinol Metab 25:c20133507

  24. Lauretani F, Maggio M, Valenti G, Dall’Aglio E, Ceda GP (2010) Vitamin D in older population: new roles for this ‘classic actor’? Aging Male 13:215–232

  25. Li H, Weng P, Najarro K, Xue QX, Semba RD, Margolick JB, Leng SX (2014) Chronic CMV infection in older women: longitudinal comparisons of CMV DNA in peripheral monocytes, anti-CMV IgG titers, serum IL-6 levels, and CMV pp 65 (NLV)-specific CD8(+) T-cell frequencies with twelve year follow-up. Exp Gerontol 54:84–89

  26. Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501

  27. Louw JA, Werbeck A, Louw ME, Kotze TJ, Cooper R, Labadarios D (1992) Blood vitamin concentrations during the acute-phase response. Crit Care Med 20:934–941

  28. Maggio M, Guralnik JM, Longo DL, Ferrucci L (2006) Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci 61:575–784

  29. Melzer D, Perry JR, Hernandez D et al (2008) A genome-wide association study identifies protein quantitative trait loci (pQTLs). PLoS Genet 4:e1000072

  30. Miller RR, Hicks GE, Shardell MD, Cappola AR, Hawkes WG, Yu-Yahiro JA, Keegan A, Magaziner J (2007) Association of serum vitamin D levels with inflammatory response following hip fracture: the Baltimore Hip Studies. J Gerontol A Biol Sci Med Sci 62:1402–1406

  31. Ngo DT, Sverdlov AL, McNeil JJ, Horowitz JD (2010) Does Vitamin D modulate asymmetricdimethylarginine and C-reactive protein concentrations? Am J Med 123:335–341

  32. Owczarek D, Cibor D, Głowacki MK, Cieśla A, Mach P (2012) TNF-α and soluble forms of TNF receptors 1 and 2 in the serum of patients with Crohn’s disease and ulcerative colitis. Pol Arch Med Wewn 122:616–623

  33. Peterson CA, Heffernan ME (2008) Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. J Inflamm (Lond) 5:10

  34. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334

  35. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC (1983) 1,25-Dihydroxyvitamin D3 receptors in human leukocytes. Science 221:1181–1183

  36. Querfeld U (2013) Vitamin D and inflammation. Pediatr Nephrol 28:605–610

  37. Reid D, Toole BJ, Knox S, Talwar D, Harten J, O’Reilly DS, Blackwell S, Kinsella J, McMillan DC, Wallace AM (2011) The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr 93:1006–1011

  38. Reyman M, Verrijn Stuart AA, van Summeren M, Rakhshandehroo M, Nuboer R, de Boer FK, van den Ham HJ, Kalkhoven E, Prakken B, Schipper HS (2013) Vitamin D deficiency in childhood obesity is associated with high levels of circulating inflammatory mediators, and low insulin sensitivity. Int J Obes (Lond) 38:46–52

  39. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96:53–58

  40. Rostkowska-Nadolska B, Sliupkas-Dyrda E, Potyka J, Kusmierz D, Fraczek M, Krecicki T, Kubik P, Zatonski M, Latocha M (2010) Vitamin D derivatives: calcitriol and tacalcitol inhibits interleukin-6 and interleukin-8 expression in human nasal polyp fibroblast cultures. Adv Med Sci 55:86–92

  41. Shea MK, Booth SL, Massaro JM et al (2008) Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol 167:313–320

  42. Siris ES, Miller PD, Barrett-Connor E, Faulkner KG, Wehren LE, Abbott TA, Berger ML, Santora AC, Sherwood LM (2001) Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. JAMA 2815-2822

  43. Stenholm S, Maggio M, Lauretani F, Bandinelli S, Ceda GP, Di Iorio A, Giallauria F, Guralnik JM, Ferrucci L (2010) Anabolic and catabolic biomarkers as predictors of muscle strength decline: the InCHIANTI study. Rejuvenation Res 13:3–11

  44. Suzuki Y, Ichiyama T, Ohsaki A, Hasegawa S, Shiraishi M, Furukawa S (2009) Anti-inflammatory effect of 1alpha,25-dihydroxyvitamin D(3) in human coronary arterial endothelial cells: Implication for the treatment of kawasaki disease. J Steroid Biochem Mol Biol 113:134–138

  45. Tenth Special Report to the U.S. Congress on Alcohol and Health from the Secretary of Health and Human Services. U.S. Department of Health and Human Services. Washington, DC: National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism (NIAAA); June 2000. NIH publication no. 00-1583

  46. Thorand B, Zierer A, Huth C, Linseisen J, Meisinger C, Roden M, Peters A, Koenig W, Herder C (2011) Effect of serum 25-hydroxyvitamin D on risk for type 2 diabetes may be partially mediated by subclinical inflammation: results from the MONICA/KORA Augsburg study. Diabetes Care 34:2320–2322

  47. Vilarrasa N, Vendrell J, Maravall J, Elío I, Solano E, San José P, García I, Virgili N, Soler J, Gómez JM (2010) Is plasma 25(OH) D related to adipokines, inflammatory cytokines and insulin resistance in both a healthy and morbidly obese population? Endocrine 38:235–242

  48. Wareham NJ, Jakes RW, Rennie KL, Mitchell J, Hennings S, Day NE (2002) Validity and repeatability of the EPIC-Norfolk Physical Activity Questionnaire. Int J Epidemiol 31:168–174

  49. Wu S, Liao AP, Xia Y, Li YC, Li JD, Sartor RB, Sun J (2010) Vitamin D receptor negatively regulates bacterial-stimulated NF-kappaB activity in intestine. Am J Pathol 177:686–697

  50. Zebaze RM, Ghasem-Zadeh A, Bohte A, Iuliano-Burns S, Mirams M, Price RI, Mackie EJ, Seeman E (2010) Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet 375:1729–1736

  51. Zuliani G, Galvani M, Maggio M, Volpato S, Bandinelli S, Corsi AM, Lauretani F, Cherubini A, Guralnik JM, Fellin R, Ferrucci L (2010) Plasma soluble gp130 levels are increased in older subjects with metabolic syndrome. The role of insulin resistance. Atherosclerosis 213:319–324

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Acknowledgments

We acknowledge Maurizio Conca, Pasquale Rosanova, and Maria Teresa Zanelli for their technical support.

The InCHIANTI Study was supported as a “targeted project” (ICS 110.1/RS97.71) by the Italian Ministry of Health and in part by the US National Institute on Aging (Contracts N01-AG-916413 and N01-AG-821336), and by the Intramural Research Program of the US National Institute on Aging (Contracts 263 MD 9164 13 and 263 MD 821336). None of the sponsoring institutions interfered with the collection, analysis, presentation, or interpretation of the data reported here. None of the authors had a conflict of interest.

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Correspondence to Marcello Maggio.

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De Vita, F., Lauretani, F., Bauer, J. et al. Relationship between vitamin D and inflammatory markers in older individuals. AGE 36, 9694 (2014). https://doi.org/10.1007/s11357-014-9694-4

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Keywords

  • Vitamin D
  • Inflammation
  • Inflammatory markers
  • Elderly subjects