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