THU0078 Antiarthritic effect of salbutamol alone and in combination with pentoxyphiline on adjuvant arthritis in rats
Authors: R Bradunaite, E Bernotiene, L Leonaviciene, D Vaitkiene
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> 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.<sup>1,2</sup> Elevation of intracellular cAMP reduces the production of IL-12 and TNF, the important cytokines in the pathogenesis of rheumathoid arthritis (RA). <h3>Objectives</h3> 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. <h3>Methods</h3> 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). <h3>Results</h3> S significantly (p &lt; 0,02) reduced joint swelling by 38,3% at the end of experiment. Combined treatment with S+P was more effective and significantly (p &lt; 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 &lt; 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 &lt; 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. <h3>Conclusion</h3> 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. <h3>References</h3> 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