Background The beta-2 ?adrenergic agonist salbutamol (S) and the phosphodiesterase inhibitor pentoxifylline (P) are reported to be the elevators of cAMP and the suppressors of Th1 response.1,2 Elevation of intracellular cAMP reduces the production of IL-12 and TNF, the important cytokines in the pathogenesis of rheumathoid arthritis (RA).
Objectives To evaluate the antiarthritic effect of S alone and in combination with P on the model of RA in animals – the expressed adjuvant arthritis (AA) in rats.
Methods Experiment was performed on 30 female Lewis rats with AA induced by a single subplantar injection of 0,1 ml of complete Freud’s adjuvant into the left hind paw. On day 8 of experiment, rats were assigned into 3 groups with the similar mean scores of joint swelling and the treatment with S (1st group) and S+P (2nd) was started. Control group (3rd) received 1ml of starch gel. Drugs were prepared as the suspension in 1% starch gel and administered intragastrically 5 times a week in a volume of 1 ml in following doses: S ? 8,5 mg/kg and P ? 500 mg/kg. The duration of treatment ? 2 weeks. Body weight and joint swelling were monitored 3 times a week. Haematological and pathomorphological changes were evaluated at the end of experiment (day 23).
Results S significantly (p < 0,02) reduced joint swelling by 38,3% at the end of experiment. Combined treatment with S+P was more effective and significantly (p < 0,02–0,01) diminished joint swelling starting at day 18 (by 36%) till the end of experiment (by 44%). Polyarthritis developed in 70% of animals treated with S, 60% – with S+P and 90% – of control group. The marked improvement (p < 0,02) of blood indices was observed in the both treated groups as compared to the control, but was more expressed using combined therapy (ESR lower by 47,8% and 56,47% and the count of leukocytes by 30,8% and 36,2%). Toxic effect of drugs on liver was not observed. S+P suppressed hepatic stroma inflammatory infiltration with lymphocytes (p < 0,05). Pathomorphological examination showed marked positive effect of both kinds of treatment on synovia, soft periarticular tissues and cartilage, but it was more expressed under the combined treatment.
Conclusion The obtained results allow to conclude that S alone and its combination with P had a pronounced antiarthritic effect, showed no toxicity and were well tolerated by animals. These results are in agreement with our previous results, where treatment with S or P separately also exerted antiarthritic effect. Pathomorphological examination at the end of the study demonstrated reduced joint swelling in both treated groups, but the combined therapy with S+P was more effective.
Malfait AM, Malik AS, Marinova-Mutafchieva L, et al. The beta 2-adrenergic agonist Salbutamol is a potent supressor of established collagen-induced arthritis: mechanisms of action. J Immunol. 1999;162:6278–83
Moller DR, Wysocka M, Greenlee BM, et al. Inhibition of human IL-12 production by pentoxifylline. Immunology 1997;91:197
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