roquinimex and Arthritis

The quinoline-3-carboxamide, Linomide, has been shown to possess potent immunomodulatory activity. We have evaluated the effect of Linomide in the type II collagen induced arthritis in mice. Treatment with Linomide (1.25-80 mg/kg/day) from the day of immunization strongly suppressed the arthritic response. On the other hand, initiation of treatment (20-80 mg/kg/day) at the onset of arthritis resulted in an increased severity of the arthritis. These potent and contradictory effects of Linomide, depending on treatment regime, indicates that central immuno-regulatory functions are affected and that this compound may be a useful tool for the understanding of autoimmune mechanisms.

Topics: Adjuvants, Immunologic; Animals; Antibodies; Arthritis; Arthritis, Experimental; Collagen; Hydroxyquinolines; Male; Mice; Mice, Inbred DBA; Time Factors

The effects of the immunomodulatory drug Linomide (LS-2616) have been investigated on two variants of collagen-induced arthritis (CIA) in Lewis rats, i.e. arthritis induced either with heterologous (bovine) or with homologous (rat) collagen type II (CII). Treatment with Linomide from the day of immunization (prophylactic) had a mild ameliorative effect on the severity of arthritis in the heterologous CIA, while the homologous CIA was strongly augmented. In both models, Linomide treatment caused a more severe arthritis when given from onset of clinical signs of disease and onwards (therapeutic). Serum antibody levels to CII were significantly decreased by prophylactic Linomide treatment in rats immunized with heterologous CII, while elevated levels of anti-rat CII antibodies were seen in the homologous model. No effect on antibody levels was seen with the therapeutic treatment regime. The opposing effects of prophylactic treatment with Linomide in heterologous versus homologous CIA indicate that the immune response to an autoantigen may be regulated differently from that to a foreign antigen. These results further strengthen the view that heterologous and homologous CIA should be regarded as separate experimental models, and that the studies on homologous CIA may represent a novel approach for future studies of autoimmune responses and evaluation of anti-rheumatic drugs.

Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Arthritis; Autoantibodies; Autoantigens; Collagen; Female; Hydroxyquinolines; Rats