Treatment of adjuvant-induced arthritis by oral, administration of mycobacterial Hsp65 during disease

Objective, Oral administration of antigen prior to disease induction has be en shown to induce peripheral tolerance in several experimental autoimmune diseases, However, the clinical benefit of pretreatment with antigens is li mited. The aim of this study was to investigate whether adjuvant- induced a rthritis (AIA)could be treated-by oral administration of mycobacterial heat -shock protein 65 (Hsp65) during ongoing disease. Methods. AIA was induced in Lewis rats by immunization with Mycobacterium t uberculosis in Freund's incomplete adjuvant, Oral feeding of Hsp65 in the p resence or absence of soybean trypsin inhibitor (SBTI) was started on day 1 1 after immunization. Arthritis was monitored visually, and joint pathology was examined radiologically, Results, Oral treatment with Hsp65 during ongoing disease significantly red uced the activity of AIA. However, treatment with Hsp65 was only successful when SBTI was coadministered to prevent breakdown of the Hsp65, The benefi cial effect of Hsp65/SBTI treatment during AIA was also represented by a cl ear reduction of articular destruction,as visualized by radiography, Moreov er, feeding Hsp65/SBTI resulted in a lower number of both spleen and mesent eric lymph node (MLN) cells expressing the costimulatory molecule CD80 (B7- 1), The number of cells expressing CD86 (B7-2) was not altered, Furthermore , MLN cells from AIA animals treated with Hsp65/SBTI contained a lower numb er of T cells expressing the activation marker CD134 (Ox-40), In addition, treatment with Hsp65/ SBTI was accompanied by an increased proliferative re sponse of spleen cells to the Hsp65 antigen in vitro; Moreover, Hsp65/SBTI- treated rats showed less Hsp65-specific interferon-gamma and increased prod uction of interleukin-10. Conclusion. Ongoing AIA activity can be seduced by oral administration of H sp65 only when protein breakdown in the gastrointestinal tract is inhibited .