EFFECT OF CAFFEINE IN EXPERIMENTAL MODEL OF RHEUMATOID ARTHRITIS IN RATS
Keywords:
Rheumatoid arthritis, CaffeineAbstract
Objective: Primary objective of this study was to evaluate anti-inflammatory effect of caffeine in complete Freund's adjuvant model of rheumatoid arthritis. Secondary objective was to compare the topical anti-inflammatory action with systemic action of caffeine and to minimize many psychotropic effect of caffeine in normal individual or arthritic patient due to systemic administration and more emphasis on topical use of caffeine as an anti-inflammatory (TNF-α blockers).
Methods: Arthritis was induced by a single sub-plantar injection (0.1 ml) of CFA into the left hind paw. Rats were treated with dexamethasone (0.05 mg/kg, p. o.), caffeine (20 and 50 mg/kg, p. o.) and caffeine gel (3% and 7% topical) from day 0 to day 12. Efficacy was evaluated by change in paw volume, serum C-reactive protein (CRP), estimation of serum rheumatoid factor (RF), arthritis index, and body weight and by histopathology of synovial joint.
Results: CFA showed significantly (p < 0.001) higher paw volume, CRP, RF and arthritic index as compared to caffeine 20 mg/kg, caffeine 50 mg/kg, caffeine gel 3% and caffeine gel 7% treated animals. It was observed that topical caffeine gel (3% and 7%) suppressed paw volume, CRP, RF and arthritic index in a more statistically significant manner compared to oral caffeine solutions (20 mg/kg and 50 mg/kg).
Conclusion: Topical caffeine gel (3% and7%) shows more significant anti-inflammatory effect as compared to oral caffeine solution (20 mg/kg and 50 mg/kg).
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References
Mutru O, Laakso M, Isomaki H, Koota K. Ten year mortality and causes of death in patients with rheumatoid arthritis. Br Med J 1985;290:1797-9.
Brennan FM, McInnes IB. Evidence that cytokines plays a role in rheumatoid arthritis. J Clin Invest 2008;118:3537-45.
Haverslag R, Pasterkamp GHI. Targeting adhesion molecules in cardiovascular disorders. Cardiovasc Hematol Disord Drug Targets 2008;8:252-60.
Commins SP, Borish LJWS. Immunologic messenger molecules: cytokines, interferons, and chemokines. J Allergy Clin Immunol 2010;125:s53-s72.
Dayer JM, Beutler B, Cerami A. Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J Exp Med 1985;162Suppl 6:2163-8.
Cassim B, Mody G, Bhoola K. Kallikrein cascade and cytokines in inflamed joints. Pharmacol Ther 2002;94(1, Suppl 2):1-34.
Horrigan LA, Kelly JP, Connor TJ. Caffeine suppresses TNF-alpha production via activation of the cyclic AMP/protein kinase a pathway. Int Immunopharmacol 2004;4(10, Suppl 11):1409-17.
Van Furth AM, Seijmonsbergen EM, Langermans JA, van der Meide PH, van Furth R. Effect of xanthine derivates and dexamethasone on Streptococcus pneumoniae-stimulated production of tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta), and IL-10 by human leukocytes. Clin Diagn Lab Immunol 1995;2 Suppl 6:689-92.
Zhang M, Xu YJ, Mengi SA, Arneja AS, Dhalla NS. Therapeutic potentials of pentoxifylline for treatment of cardiovascular diseases. Exp Clin Cardiol 2004;9 Suppl 2:103-11.
Lara DR. Caffeine, mental health, and psychiatric disorders. J Alzheimers Dis 2010;20 Suppl 1:S239-48.
Van Furth AM, Seijmonsbergen EM, Langermans JA, Van der Meide PH, Van Furth R. Effect of xanthine derivates and dexamethasone on Streptococcus pneumoniae-stimulated production of tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta), and IL-10 by human leukocytes. Clin Diagn Lab Immunol 1995;2 Suppl 6:689-92.
Shames BD, McIntyre RC Jr, Bensard DD, Pulido EJ, Selzman CH, Reznikov LL, et al. Suppression of tumor necrosis factor alpha production by cAMP in human monocytes: dissociation with mRNA level and independent of interleukin-10. J Surg Res 2001;99 Suppl 2:187-93.
Chavez-Valdez R, Wills-Karp M, Ahlawat R, Cristofalo EA, Nathan A, Gauda EB. Caffeine modulates TNF-alpha production by cord blood monocytes: the role of adenosine receptors. Pediatr Res 2009;65 Suppl 2:203-8.
Vierboom MP, Jonker M, TakPP, Hart BA. Preclinical models of arthritic disease in non-human primates. Drug Discov Today 2007;12(7, Suppl 8):327-35.
Shinde UA, Phadke AS, Nair AM, Mungantiwar AA, Dikshit VJ, Saraf MN. Studies on the anti-inflammatory and analgesic activity of Cedrus deodara (Roxb.) Loud. Wood oil. J Ethnopharmacol 1999;65 Suppl 1:21-7.
Tsai CC, Lin CC. Anti-inflammatory effects of Taiwan folk medicine ‘Teng-Khia-U’ on carrageenan-and adjuvant-induced paw edema in rats. J Ethnopharmacol 1999;64 Suppl 1:85-9.
Wang H, Yang H, Czura CJ, Sama AE, Tracey KJ. HMGB1 as a late mediator of lethal systemic inflammation. Am J Respir Crit Care Med 2001;164:1768-73.
Song YW, Kang EH. The pathogenic role of rheumatoid factor in rheumatoid arthritis. Int J Clin Rheumtol 2010;5 Suppl 6:651-8.
Notley CA, Brown MA, Wright GP, Ehrenstein MR. Natural IgM is required for suppression of inflammatory arthritis by apoptotic cells. J Immunol 2011;186 Suppl 8:4967-72.
Colpaert FC. Evidence that adjuvant arthritis in the rat is associated with chronic pain. Pain 1987;28 Suppl 2:201-22.