BIPHASIC EFFECT OF INTERFERON-GAMMA IN MURINE COLLAGEN-INDUCED ARTHRITIS

Interferon-gamma (IFN-gamma) exerts both enhancing and suppressing inf luences on collagen-induced arthritis (CIA), depending on the route an d protocol of administration. To study the role of IFN-gamma on the au toimmune process of CIA, we treated DBA/1 mice with two different rat monoclonal antibodies (mAb) to murine IFN-gamma. Treatments, given twi ce weekly for 4 weeks, consisted of intraperitoneal injections of eith er mAb. In early treatments, starting from the day of immunization wit h type II collagen (CII), the severity of arthritis was reduced in bot h groups of anti-IFN-gamma-treated mice compared with control groups. Moreover, anti-CII antibody levels decreased in the sera of these mice . CIA was also down-regulated in mice treated from days 14 or 28 post immunization. In contrast, late treatments with anti-IFN-gamma mAb eit her induced aggravating effects, or did not affect the course of the d isease. On the other hand, administration of high doses (8 x 10(4) U t hree times/week) of rat recombinant IFN-gamma exerted a transient incr ease of CIA severity. These findings suggest that IFN-gamma may play a critical role during both the induction and the course of CIA, first enhancing the immune response, and then regulating the arthritis proce ss.