Upregulated Monocytic Expression of CXC Chemokine Ligand 10 (CXCL-10) and Its Relationship with Serum Interleukin-6 Levels in the Syndrome of Frailty

Overview

Journal Cytokine

Specialties Allergy & Immunology
Biology

Date 2009 Apr 4

PMID 19342252

Citations 50

Authors

Tao Qu

Huanle Yang

Jeremy D Walston

Neal S Fedarko

Sean X Leng

Affiliations

Soon will be listed here.

Abstract

Frailty is an important geriatric syndrome that predicts disability and mortality. Substantial evidence suggests inflammation marked by elevated IL-6 levels as a key pathophysiologic factor that contributes to frailty. CXCL-10, a potent pro-inflammatory chemokine, has increased levels with age and is implicated in several inflammatory conditions. To better understand molecular mechanisms of inflammation activation in frailty, we evaluated monocytic expression of CXCL-10 and other inflammatory pathway genes by pathway-specific gene array analysis and quantitative RT-PCR. Frailty status was determined by the validated criteria. Sixteen pairs of community-dwelling frail and age-, race-, and sex-matched non-frail participants (mean age 83 years, range 72-94) completed the study. Here we report that frail participants had higher CXCL-10 expression levels than matched non-frail controls (1.05+/-0.88 versus 0.53+/-0.39, p=0.04). CXCL-10 expression correlated with IL-6 levels only in frail participants (Spearman correlation coefficient r=0.52, p=0.03). Furthermore, frailty-associated CXCL-10 upregulation was highly correlated with IL-6 elevation, both measured by frail-over-non-frail ratios (r=0.93, p<0.0001). These findings suggest upregulated monocytic expression of CXCL-10 as an important molecular mechanism that contributes to inflammation activation in frail older adults. Therapeutic implications include potential development of CXCL-10-based interventional strategies for the prevention and treatment of frailty in older adults.

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References

Antonelli A, Rotondi M, Fallahi P, Romagnani P, Ferrari S, Buonamano A . High levels of circulating CXC chemokine ligand 10 are associated with chronic autoimmune thyroiditis and hypothyroidism. J Clin Endocrinol Metab. 2004; 89(11):5496-9. DOI: 10.1210/jc.2004-0977. View

Leng S, Xue Q, Tian J, Walston J, Fried L . Inflammation and frailty in older women. J Am Geriatr Soc. 2007; 55(6):864-71. DOI: 10.1111/j.1532-5415.2007.01186.x. View

De Fanis U, Wang G, Fedarko N, Walston J, Casolaro V, Leng S . T-lymphocytes expressing CC chemokine receptor-5 are increased in frail older adults. J Am Geriatr Soc. 2008; 56(5):904-8. PMC: 2662852. DOI: 10.1111/j.1532-5415.2008.01673.x. View

Fried L, Ferrucci L, Darer J, Williamson J, Anderson G . Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004; 59(3):255-63. DOI: 10.1093/gerona/59.3.m255. View

Franciotta D, Martino G, Zardini E, Furlan R, Bergamaschi R, Andreoni L . Serum and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies. J Neuroimmunol. 2001; 115(1-2):192-8. DOI: 10.1016/s0165-5728(01)00261-2. View

Neville L, Mathiak G, Bagasra O . The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. Cytokine Growth Factor Rev. 1998; 8(3):207-19. DOI: 10.1016/s1359-6101(97)00015-4. View

Fried L, Hadley E, Walston J, Newman A, Newman A, Guralnik J . From bedside to bench: research agenda for frailty. Sci Aging Knowledge Environ. 2005; 2005(31):pe24. DOI: 10.1126/sageke.2005.31.pe24. View

Fried L, Tangen C, Walston J, Newman A, Hirsch C, Gottdiener J . Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001; 56(3):M146-56. DOI: 10.1093/gerona/56.3.m146. View

Nicoletti F, Conget I, DI Mauro M, Di Marco R, Mazzarino M, Bendtzen K . Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease. Diabetologia. 2002; 45(8):1107-10. DOI: 10.1007/s00125-002-0879-5. View

10.

Wildbaum G, Netzer N, Karin N . Plasmid DNA encoding IFN-gamma-inducible protein 10 redirects antigen-specific T cell polarization and suppresses experimental autoimmune encephalomyelitis. J Immunol. 2002; 168(11):5885-92. DOI: 10.4049/jimmunol.168.11.5885. View

11.

Maggio M, Guralnik J, Longo D, Ferrucci L . Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci. 2006; 61(6):575-84. PMC: 2645627. DOI: 10.1093/gerona/61.6.575. View

12.

Sadeghi H, Schnelle J, Thoma J, Nishanian P, Fahey J . Phenotypic and functional characteristics of circulating monocytes of elderly persons. Exp Gerontol. 2000; 34(8):959-70. DOI: 10.1016/s0531-5565(99)00065-0. View

13.

Schmaltz H, Fried L, Xue Q, Walston J, Leng S, Semba R . Chronic cytomegalovirus infection and inflammation are associated with prevalent frailty in community-dwelling older women. J Am Geriatr Soc. 2005; 53(5):747-54. DOI: 10.1111/j.1532-5415.2005.53250.x. View

14.

Miles E, Rees D, Banerjee T, Cazzola R, Lewis S, Wood R . Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations. Atherosclerosis. 2006; 196(1):298-305. DOI: 10.1016/j.atherosclerosis.2006.11.002. View

15.

Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T . Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc Natl Acad Sci U S A. 1993; 90(21):10193-7. PMC: 47740. DOI: 10.1073/pnas.90.21.10193. View

16.

Paganelli R, Di Iorio A, Cherubini A, Lauretani F, Mussi C, Volpato S . Frailty of older age: the role of the endocrine--immune interaction. Curr Pharm Des. 2006; 12(24):3147-59. DOI: 10.2174/138161206777947533. View

17.

De Martinis M, Franceschi C, Monti D, Ginaldi L . Inflammation markers predicting frailty and mortality in the elderly. Exp Mol Pathol. 2006; 80(3):219-27. DOI: 10.1016/j.yexmp.2005.11.004. View

18.

Leng S, Chaves P, Koenig K, Walston J . Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc. 2002; 50(7):1268-71. DOI: 10.1046/j.1532-5415.2002.50315.x. View

19.

Rotondi M, Rosati A, Buonamano A, Lasagni L, Lazzeri E, Pradella F . High pretransplant serum levels of CXCL10/IP-10 are related to increased risk of renal allograft failure. Am J Transplant. 2004; 4(9):1466-74. DOI: 10.1111/j.1600-6143.2004.00525.x. View

20.

Comabella M, Imitola J, Weiner H, Khoury S . Interferon-beta treatment alters peripheral blood monocytes chemokine production in MS patients. J Neuroimmunol. 2002; 126(1-2):205-12. DOI: 10.1016/s0165-5728(02)00064-4. View