ANTIRHEUMATIC ESCHERICHIA-COLI EXTRACT OM-89 INDUCES T-CELL RESPONSESTO HSP60 AND HSP70

Oral administration of E. coli extract OM-89 is used in treating RA. I t has been shown that immune reactivity to heat-shock proteins (hsp) i s involved in immunomodulation of arthritis. We evaluated the postulat ed presence and immunogenicity of hsp's in OM-89. The effects of OM-89 in experimental arthritis were analyzed. Proliferative T cell respons es to bacterial hsp60 and hsp70 were found in rats immunized with OM-8 9. And conversely, immunization with hsp antigens induced OM-89-specif ic T cell responses. Hsp70 (DnaK) was found to be a major immunogenic constituent of OM-89. Parenteral immunization with OM-89 reduces resis tance to adjuvant arthritis (AA), whereas oral administration protects against AA. Given the arthritis inhibitory effect of oral OM-89 in AA our findings suggest peripheral tolerance induced by hsp-specific reg ulatory T cells as a mode of action for OM-89 as an arthritis suppress ive oral drug. (C) 1998 Published by Elsevier Science Ltd on behalf of the International Society for Immunopharmacology.