Cytokine measurements in Brazilian postmenopausal osteoporosis patients reveal high levels of IL-8

Pablo Ramon Gualberto Cardoso, Thiago Sotero Fragoso, Alexandre Domingues Barbosa, Moacyr Jesus Barreto de Melo Rêgo, Ivan da Rocha Pitta, Angela Luzia Branco Pinto Duarte, Claudia Diniz Lopes Marques, Maira Galdino da Rocha Pitta

Abstract


Aims: Osteoporosis is a common disease that affects mostly women and has been associated with the immune system. The aims of this study were to evaluate the serum levels of inflammatory cytokines in women with postmenopausal osteoporosis and to investigate their relationship with clinical and laboratory parameters.

Methods: This study recruited patients with postmenopausal osteoporosis (osteoporosis group) and non-osteoporotic postmenopausal women (control group) matched for age. All patients and controls had their bone mineral density measured for the diagnosis of osteoporosis and answered a clinical questionnaire. Blood samples were collected for cytokine measurements. Cytokines IFN-γ, IL-1β, IL-6, IL-8, IL-9, IL-10, IL-17A, IL-22, IL-27, IL-29, IL-35, and TNF-α were measured by an enzyme-linked immunosorbent assay.

Results: Twenty-nine out of the 52 (55.8%) postmenopausal osteoporosis patients showed high levels of IL-8, while no patients from the control group (n=21) showed IL-8 values above the detection limit (p<0.0001). Higher levels of IFN-γ and IL-35 were associated with the control group, with p values of 0.0053 and 0.0214, respectively. In the osteoporosis group, IFN-γ was correlated with longer duration of smoking (p=0.003), IFN-γ and IL-6 were correlated with higher age at menarche (p=0.0454 and p=0.0380), IL-22 was correlated with duration of menopause (p=0.0289) and IL-9 with calcium intake (p=0.019). The other cytokines showed no association or correlation with clinical parameters.

Conclusions: IL-8 was elevated in the serum of patients with postmenopausal osteoporosis, perhaps because it may trigger osteoclast activation and bone wear in osteoporosis. Higher levels of IFN-γ, IL-6, IL-9, IL-22, IL-27, and IL-35 were also associated with the osteoporosis group patients and showed significant correlation with clinical parameters in postmenopausal osteoporosis.

Keywords


interleukins; age-related osteoporosis; osteoporosis, postmenopausal; vitamin D; bone density.

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References


Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA. Matrix-embedded cells control osteoclast formation. Nat Med. 2011 Sep 11;17(10):1235-41. http://dx.doi.org/10.1038/nm.2448

Melton LJ 3rd, Thamer M, Ray NF, Chan JK, Chesnut CH 3rd, Einhorn TA, Johnston CC, Raisz LG, Silverman SL, Siris ES. Fractures attributable to osteoporosis: report from the National Osteoporosis Foundation. J Bone Miner Res. 1997 Jan;12(1):16-23. http://dx.doi.org/10.1359/jbmr.1997.12.1.16

Garriguet D. Bone health: osteoporosis, calcium and vitamin D. Health Rep. 2011 Sep;22(3):7-14.

Feng W, Xia W, Ye Q, Wu W. Osteoclastogenesis and osteoimmunology. Front Biosci (Landmark Ed). 2014 Jan 1;19:758-67. http://dx.doi.org/10.2741/4242

Takayanagi H. Inflammatory bone destruction and osteoimmunology. J Periodontal Res. 2005 Aug;40(4):287-93. http://dx.doi.org/10.1111/j.1600-0765.2005.00814.x

Zupan J, Komadina R, Marc J. The relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory cytokines differs in human osteoporotic and osteoarthritic bone tissues. J Biomed Sci. 2012 Mar 1;19:28. http://dx.doi.org/10.1186/1423-0127-19-28

Takayanagi H, Kim S, Koga T, Taniguchi T. Stat1-mediated cytoplasmic attenuation in osteoimmunology. J Cell Biochem. 2005 Feb 1;94(2):232-40. http://dx.doi.org/10.1002/jcb.20316

Takayanagi H. Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol. 2009 Dec;5(12):667-76. http://dx.doi.org/10.1038/nrrheum.2009.217

Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994;843:1-129.

Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol. 2009 Feb;19(2):73-8. http://dx.doi.org/10.1016/j.annepidem.2007.12.001

Rocha Junior LF, Rêgo MJ, Cavalcanti MB, Pereira MC, Pitta MG, Oliveira PS, Gonçalves SM, Duarte AL, Lima Mdo C, Pitta Ida R, Pitta MG. Synthesis of a novel thiazolidinedione and evaluation of its modulatory effect on IFN- γ , IL-6, IL-17A, and IL-22 production in PBMCs from rheumatoid arthritis patients. Biomed Res Int. 2013;2013:926060. http://dx.doi.org/10.1155/2013/926060

Marsh D, Woolf A, Akesson K. Osteoporosis and fragility fractures. Preface. Best Pract Res Clin Rheumatol. 2013 Dec;27(6):709-10. http://dx.doi.org/10.1016/j.berh.2014.03.001

Lane NE. Osteoporosis: yesterday, today and tomorrow. Rheumatology (Oxford). 2011 Jul;50(7):1181-3. http://dx.doi.org/10.1093/rheumatology/ker147

Hébert CA, Luscinskas FW, Kiely JM, Luis EA, Darbonne WC, Bennett GL, Liu CC, Obin MS, Gimbrone MA Jr, Baker JB. Endothelial and leukocyte forms of IL-8. Conversion by thrombin and interactions with neutrophils. J Immunol. 1990 Nov 1;145(9):3033-40.

Capellino S, Cosentino M, Luini A, Bombelli R, Lowin T, Cutolo M, Marino F, Straub RH. Increased expression of dopamine receptors in synovial fibroblasts from patients with rheumatoid arthritis: inhibitory effects of dopamine on interleukin-8 and interleukin-6. Arthritis Rheumatol. 2014 Oct;66(10):2685-93. http://dx.doi.org/10.1002/art.38746

Khosropanah H, Sarvestani EK, Mahmoodi A, Golshah M. Association of IL-8 (-251 a/t) gene polymorphism with clinical parameters and chronic periodontitis. J Dent (Tehran). 2013 May;10(4):312-8.

Parker SE, Troisi R, Wise LA, Palmer JR, Titus-Ernstoff L, Strohsnitter WC, Hatch EE. Menarche, menopause, years of menstruation, and the incidence of osteoporosis: the influence of prenatal exposure to diethylstilbestrol. J Clin Endocrinol Metab. 2014 Feb;99(2):594-601. http://dx.doi.org/10.1210/jc.2013-2954

Cordoba-Rodriguez R, Frucht DM. IL-23 and IL-27: new members of the growing family of IL-12-related cytokines with important implications for therapeutics. Expert Opin Biol Ther. 2003 Aug;3(5):715-23. http://dx.doi.org/10.1517/14712598.3.5.715

Kamiya S, Nakamura C, Fukawa T, Ono K, Ohwaki T, Yoshimoto T, Wada S. Effects of IL-23 and IL-27 on osteoblasts and osteoclasts: inhibitory effects on osteoclast differentiation. J Bone Miner Metab. 2007;25(5):277-85. http://dx.doi.org/10.1007/s00774-007-0766-8

Fitzgerald DC, Rostami A. Therapeutic potential of IL-27 in multiple sclerosis? Expert Opin Biol Ther. 2009 Feb;9(2):149-60. http://dx.doi.org/10.1517/14712590802646936

Moon SJ, Park JS, Heo YJ, Kang CM, Kim EK, Lim MA, Ryu JG, Park SJ, Park KS, Sung YC, Park SH, Kim HY, Min JK, Cho ML. In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced arthritis. Exp Mol Med. 2013 Oct 4;45:e46. http://dx.doi.org/10.1038/emm.2013.89

Babaloo Z, Yeganeh RK, Farhoodi M, Baradaran B, Bonyadi M, Aghebati L. Increased IL-17A but decreased IL-27 serum levels in patients with multiple sclerosis. Iran J Immunol. 2013 Mar;10(1):47-54.

Murugaiyan G, Saha B. IL-27 in tumor immunity and immunotherapy. Trends Mol Med. 2013 Feb;19(2):108-16. http://dx.doi.org/10.1016/j.molmed.2012.12.002

Kalliolias GD, Zhao B, Triantafyllopoulou A, Park-Min KH, Ivashkiv LB. Interleukin-27 inhibits human osteoclastogenesis by abrogating RANKL-mediated induction of nuclear factor of activated T cells c1 and suppressing proximal RANK signaling. Arthritis Rheum. 2010 Feb;62(2):402-13.

Zhao L, Jiang Z, Jiang Y, Ma N, Zhang Y, Feng L, Wang K. IL-22+ CD4+ T cells in patients with rheumatoid arthritis. Int J Rheum Dis. 2013 Oct;16(5):518-26 http://dx.doi.org/10.1111/1756-185X.12099

Souza JM, Matias BF, Rodrigues CM, Murta EF, Michelin MA. IL-17 and IL-22 serum cytokine levels in patients with squamous intraepithelial lesion and invasive cervical carcinoma. Eur J Gynaecol Oncol. 2013;34(5):466-8.

Lin J, Yue LH, Chen WQ. Decreased plasma IL-22 levels and correlations with IL-22-producing T helper cells in patients with new-onset systemic lupus erythematosus. Scand J Immunol. 2014 Feb;79(2):131-6. http://dx.doi.org/10.1111/sji.12135

Commins S, Steinke JW, Borish L. The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. J Allergy Clin Immunol. 2008 May;121(5):1108-11. http://dx.doi.org/10.1016/j.jaci.2008.02.026

Sioka C, Fotopoulos A, Georgiou A, Xourgia X, Papadopoulos A, Kalef-Ezra JA. Age at menarche, age at menopause and duration of fertility as risk factors for osteoporosis. Climacteric. 2010 Feb;13(1):63-71. http://dx.doi.org/10.3109/13697130903075337

Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. http://dx.doi.org/10.1210/jc.2011-0385




DOI: http://dx.doi.org/10.15448/1980-6108.2016.3.23399

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