Relationship between Plasma Levels of Homocysteine and Pro-Inflammatory Cytokines in Patients with Rheumatoid Arthritis

Year 2016, Volume: 7 Issue: 2, 163 - 167, 16.06.2016

Ayşe Balkarli

https://doi.org/10.5799/ahinjs.01.2016.02.0590

Abstract

Objective: The aim of the study was to investigate
levels of homocysteine (Hcy), folate, vitamin B12, interleukin-6 (IL-6)
and Tumor necrosis factor-alpha (TNF-α) and to assess relationship
between Hcy levels and inflammatory mediators including IL-6 and TNF-α
in untreated patients with rheumatoid arthritis (RA).

Methods: The study included 55 women including 30
newly diagnosed and untreated female RA patients and 25 age-matched
healthy individuals as controls.

Results: Erythrocyte sedimentation rate (ESH),
C-reactive protein (CRP), IL-6 and TNF-α levels were significantly
higher in RA patients than controls (p<0.05). Homocysteine levels
were higher in RA group when compared to controls; how­ever, folate and
vitamin B12 levels were not different between groups (p>0.05). There
were no significant correlations between Hcy levels and acute phase
reactants or inflammatory mediators (p>0.05).

Conclusion: Both mediators such as IL-6 and TNF-α and
hyper-homocysteinemia are associated with atherosclerotic cardiovascular
diseases. There was no significant correlation between Hcy levels and
inflammatory mediators, although levels of these molecules were elevated
in RA. Both inflammatory mediators and Hcy may cause an increase in
athero­sclerotic cardiovascular disorders through diverse pathways. J Clin Exp Invest 2016; 7 (2): 163-167

Keywords

Rheumatoid arthritis, IL-6, homocysteine, TNF- α

References

• 1. Wasserman AM. Diagnosis and management of rheumatoid arthritis. Am Fam Physician. 2011;84:1245-52. 2. Karahan AY, Bagcaci S, Salbas E, et al. The assessment of knowledge level about their disease in patients with rheu - matoid arthritis. J Clin Exp Invest. 2014;5:429-34. 3. Tuna Z, Oskay D, Onbulak D and Mercan R. Analysis of the effects of hospitalization on fine hand functions compared to gross grip in patients with rheumatoid arthritis. J Clin Exp Invest. 2015;6:228-32. 4. Cooles FAH, Isaacs JD. Pathophysiology of rheumatoid ar - thritis. Curr Opin Rheumatol. 2011;23:233-40. 5. Schett G, Teitelbaum SL. Osteoclasts and arthritis. J Bone Miner Res. 2009;24:1142-6. 6. Nishimoto N, Yoshizaki K, Miyasaka N, et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6rRe - ceptor antibody. Am Coll Rheumatol. 2004;50:1761-9. 7. Tiftikci A, Ozdemir A, Tarcin O, et al. Influence of serum folic acid levels on plasma homocysteine concentra - tions in patients with rheumatoid arthritis. Rheumatol Int. 2006;26:191-4. 8. Turiel M, Sitia S, Atzeni F, et al. The heart in rheumatoid arthritis. Autoimmun Rev. 2010;9:414-8. 9. Maradıt-Kremers H, Nicola PJ, Ccrowson CS, et al. Cardio - vascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2005;52:722-32. 10. Willers J, Hahn A. Cardiovascular risk in patients with rheumatoid arthritis: assessment of several traditional risk parameters and a German risk score model. Rheumatol Int. 2012;32:3741-9. 11. Galiutina O, Bychak OV. Relationship of silent myocardial ischiemia with the course of rheumatoid arthritis and hyper - homocysteinemia. Lik Sprava. 2011;1:48-52. 12. Colak A, Avci R, Yener S, et al. Relationship between subclinical hypothyroidism and serum homocysteine con - centration in premenopausal women. J Clin Exp Invest. 2013;4:293-7. 13. Erşan İ, Öztürk BT, Kamış Ü, et al. Comparison of plasma homocysteine levels in patients with type 2 diabetes mel - litus with normal subjects. J Clin Exp Invest. 2012;3:235-9. 14. Turhan S, Sezer S, Erden G, et al. Plasma homocysteine concentrations and serum lipid profile as atherosclerotic risk factors in subclinical hypothyroidism. Ann Saudi Med. 2008;28:96-101. 15. Sütken E, Akalın A, Özdemir F, Çolak Ö. Lipid profile and levels of homocysteine, leptin, fibrinogen and C-reactive protein in hyperthyroid patients before and after treatment. Dicle Med J. 2009;37:1-7. 16. Vignini A, Nanetti L, Bacchetti, et al. Modification induced by homocysteine and low-density lipoprotein on human aortic endothelial cells: an in vitro study. J Clin Endocrinol Metab. 2004;89:4558-61. 17. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288:2015-22. 18. Stanger O, Herrmann W, Pietrzik K, et al. DACH-LIGA ho - mocystein (german, austrian and swiss homocysteine soci - ety): consensus paper on the rational clinical use of homo - cysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guide¬lines and recommendations. Clin Chem Lab Med. 2003;41:1392-403. 19. Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid ar - thritis classification criteria: an American College of Rheu - matology/European League Against Rheumatism collab - orative initiative. Arthritis Rheumatism. 2010;62:2569-81. 20. Mangioni AA, Jackson SHD. Homocysteine and cardiovas - cular disease: current evidence and future prospects. Am J Med. 2002;112:556-65. 21. Al-Obaidi MK, Philippou H, Stubbs PJ, et al. relation - ships between homocysteine, factor VIIa, and thrombin generation in acute coronary syndromes. Circulation. 2000;101:372-7. 22. Stanger O, Semmelrock Hj, Wonısch W, et al. Effects of folate treatment and homocysteine lowering on resistance vessel reactivity in atherosclerotic subjects. J Pharmacol Exp Ther. 2002;303:158-62. 23. Al-Obaidi-MK, Stubbs PJ, Collison P, et al. Elevated ho - mocysteine levels are associated with increased ıschemic myocardiyal ınjury in acute coronary sendromes. Am Coll Cardiol. 2000; 36: 1217-22. 24. Schroecksnadel K, Fricka B, Kaserb S, et al. Moderate hyperhomocysteinaemia and immun-activation in pa - tients with rheumatoid arthritis. Clinica Chimica Acta. 2003;338:157-164. 25. Bjornadal L, Baecklund E, Yin L, et al. Decreasing mortal - ity in patients with rheumatoid arthritis: results from a large population based cohort in Sweden, 1964-95. J Rheumatol. 2002;29:906-12. 26. Solomon DH, Karlson EW, Rimm EB, et al. Cardiovascular morbidity and mortality in women diagnosed with rheuma - toid arthritis. Circulation. 2003;107:1303-7. 27. Landewe RB, van den Borne BEEM, Breedveld FC, Di - jkmans BA. Methotrexate effects in patients with rheu - matoid arthritis with cardiovascular morbidity. Lancet. 2000;355:1616-7. 28. Choi HK, Hernan MA, Seeger JD, et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospec - tive study. Lancet. 2002;359:1173-7. 29. Szekanecz Z, Kerekes G, Der H, et al. Accelerated ath - erosclerosis in rheumatoid arthritis. Ann NY Acad Sci. 2007;1108: 349-58. 30. Park YB, Lee SK, Lee WK, et al. Lipid profiles in un - treated patients with rheumatoid arthritis. J Rheumatol. 1999;26:1701-4. 31. Yang X, Gao F, Liu Y. Association of homocysteine with immunological-inflammatory and metabolic laboratory markers and factors in relation to hyperhomocysteinaemia in rheumatoid arthritis. Clin Exp Rheumatol. 2015;33:900- 3. 32. Dimitroulas T, Sandoo A, Hodson J, et al. Associations be - tween asymmetric dimethylarginine, homocysteine, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in rheumatoid arthritis. Scand J Rheumatol. 2015;24:1-7. 33. Wallenberg-Jonsson S, Ohman ML, Dahlqvist SR. Cardio - vascular morbidity and mortality in patients with seroposi - tive rheumatoid arthritis in Northern Sweden. J Rheumatol. 1997;24:445-51. 34. Eikelboom JW, Lonn E, Genest J Jr, et al. Homocyst(e)ine and cardiovascular disease: a critical review of the epide - miologic evidence. Ann Intern Med. 1999;131:363-75. 35. Roubeno R, Dellaripa P, Nadeau RM, et al. Abnormal ho - mocysteine metabolism in rheumatoid arthritis. Arthritis Rheum.1997;40:718-22. 36. Haagsma JC, Blom JH, Van Riel PLCM, et al. Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis. 1999;58:79-84.