Cytokine measurements in Brazilian postmenopausal osteoporosis patients reveal high levels of IL-8
DOI:
https://doi.org/10.15448/1980-6108.2016.3.23399Palavras-chave:
interleucinas, osteoporose relacionada à idade, osteoporose pós-menopausa, vitamina D, densidade óssea.Resumo
Dosagem de citocinas em pacientes brasileiras com osteoporose pós-menopausa revela altos níveis de IL-8
Objetivos: A osteoporose é uma doença comum, que afeta principalmente as mulheres e tem sido associada com o sistema imune. Este estudo objetivou avaliar níveis séricos de citocinas inflamatórias em mulheres pós-menopáusicas com osteoporose, assim como investigar as suas relações com parâmetros clínicos e laboratoriais.
Métodos: Este estudo recrutou pacientes com osteoporose pós-menopausa e voluntárias sem a doença, pareadas por idade. Todas as pacientes do grupo com osteoporose e as integrantes do grupo controle passaram pelo exame de mensuração de densidade óssea para diagnosticar a doença e todas responderam a um questionário clínico. Amostras de sangue foram coletadas para as dosagens séricas. As citocinas IFN-γ, IL-1β, IL-6, IL-8, IL-9, IL-10, IL-17A, IL-22, IL-27, IL-29, IL-35 e TNF-α foram dosadas por ensaio imunoenzimático.
Resultados: Vinte e nove entre as 52 (55,8%) pacientes com osteoporose pós-menopausa mostraram altos níveis de IL-8, enquanto nenhuma integrante do grupo controle teve valores de IL-8 acima do nível de detecção do kit (p<0,0001). Altos níveis de IFN-γ and IL-35 foram associados ao grupo controle, com valores de p de 0,0053 and 0,0214 respectivamente. No grupo osteoporose, IFN-γ mostrou correlação com o tempo de duração do tabagismo (p=0,003). IFN-γ e IL-6 foram correlacionadas com a idade de ocorrência da menarca (p=0,0454 e p=0,0380). A citocina IL-22 correlacionou-se com a duração da menopausa (p=0,0289), e a IL-9 com a ingestão de mais cálcio na dieta (p=0,019). As outras citocinas dosadas não mostraram associações ou correlações com os parâmetros clínicos.
Conclusões: A IL-8 mostrou-se elevada no soro das pacientes com osteoporose pós-menopausa, talvez por atuar como um gatilho para a ativação dos osteoclastos e desgaste ósseo que ocorre na osteoporose. Níveis mais altos de IFN-γ, IL-6, IL-9, IL-22, IL-27 e IL-35 também estiveram presentes no soro das pacientes do grupo osteoporose e mostraram associações significativas com os parâmetros clínicos na osteoporose pós-menopausa.
Downloads
Referências
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