THERAPEUTIC EFFECTS OF ANTIBODIES AGAINST ADHESION MOLECULES IN MURINE COLLAGEN TYPE II-INDUCED ARTHRITIS

Adhesion molecules play important roles in immune reactions and inflam matory processes and may constitute attractive targets for immunomodul atory approaches. In this study, blocking mAbs against a series of adh esion molecules were tested for their therapeutic effect on developing arthritis in a mouse model. MAbs were given for a period of 4 weeks a t the time of exspected incidence of visible disease symptoms, i.e. 4 weeks after priming with collagen type II. A significant reduction of incidence down to values of 13% and 29% of the controls was obtained w ith mAbs against CD44 and alpha(4)-integrin, respectively, during an o bservation time of 13 weeks. MAbs against CD4 and LFA-1 resulted only in weaker, non-significant effects or a delay in the incidence. MAbs a gainst other molecules including L-selectin, ICAM-1 or VCAM-1 were not effective. The development of antibodies against collagen type II, co llagen type I, proteoglycans and the immunogen, bovine collagen type I I was affected by mAb treatment to a different extent. In this case, t he anti CD4 mAb was the most effective, followed by the anti alpha(4)- antibodies in most cases, whereas anti CD44 showed less clear effects on the development of humoral responses. In a skin delayed type hypers ensitivity model analyzed for comparision, mAbs against LFA-1/ICAM-1 a nd alpha(4)-integrin showed the largest effects on ear swelling. These data show that mAbs against several adhesion molecules are able to bl ock selectively distinct aspects of immune reactions, and that CD44 an d alpha(4)-integrins could be promising targets for an immunotherapy o f rheumatoid arthritis with receptor-interfering agents.