Abstract
In recent years, considerable efforts have been made to develop effective therapy for autoimmune diseases by specific suppression of the autoreactive immune process without affecting the remainder of the immune system. In our study we evaluated the protective effects and therapeutic potential of Mycobacterium butyricum (Mb), the causative antigen inducing adjuvant arthritis (AA), an experimental model of autoimmune disease in the rat. The antigen was administered to rats by a different route and at concentrations 10 and 100 times lower than the inducing one. Arthritis was induced by injection of 0.6 mg of Mb in paraffin oil into the hindpaw, and the severity of disease was assessed by measurement of contralateral paw swelling every three days and primary and secondary lesions were scored on an arbitrary scale after 14, 21, and 28 days. Animals were assigned to different groups and treated intraperitoneally with different doses and schedules of Mb. The administration of 60 μg of Mb every two days, starting 6 days before arthritogenic injection until the second day after, led to a significant inhibition of the arthritic process (p< 0.001 of the arthritic index). Treatment of animals with 60 μg of Mb every two days, from day 2 to day 21 after arthritis induction caused almost total suppression of lesions. However, in both treatment schedules, animals showed important signs of peritoneal inflammation. The administration of single injection of 60 or 6 μg of Mb 10 days after arthritis induction led to an inhibition of arthritic index reaching the maximum percentage on day 14 (26% and 24% with 60 and 6 μg respectively) and was able to delay the development of oedema foot volume, without signs of local inflammation. These results confirm the ability to modulate the autoimmune process even when the immunological response is far advanced, suggesting new strategies in the therapy of human autoimmune diseases.
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