chiniofon 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

A series of 4-hydroxy-3-quinolinecarboxamides has been synthesized and evaluated by the oral route as antiinflammatory agents in carrageenin-induced foot edema and adjuvant-induced arthritis and as analgesic agents in the acetic acid induced writhing test. Among the most active molecules, some have shown both analgesic and acute antiinflammatory activities. Others, such as compounds 24, 37, and 52, were only powerful peripherally acting analgesics. Compound 52, being active at 1 mg/kg (ED50), is the most potent compound in the series. Some analogues, substituted in the 2-position by an alcohol, ester, or amine function, displayed potent antiarthritic activity in the same range as that of piroxicam and were also active in acute tests of inflammation and nociception. They inhibited the activity of both cyclooxygenase and 5-lipoxygenase at micromolar concentrations. Compound 102 (RU 43526) showed potent antiarthritic activity (adjuvant-induced arthritis, ED50 = 0.7 mg/kg, po) and gastrointestinal tolerance (ED100 greater than 250 mg/kg, po) and thus it is presently undergoing an extensive pharmacological evaluation.

Topics: Amides; Analgesia; Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Experimental; Carrageenan; Cattle; Chemical Phenomena; Chemistry; Cyclooxygenase Inhibitors; Edema; Female; Hydroxyquinolines; Lipoxygenase Inhibitors; Male; Mice; Pain Measurement; Rats; Rats, Inbred Lew; Rats, Inbred Strains; Structure-Activity Relationship

The biodistributions of In-111 oxine (with and without leukocyte labeling) of Ga-67 citrate and of In-111 chloride were compared in 30 dogs with chemical and bacterial abscesses and acute joint inflammation. Serial blood samples were taken and tissues radioassayed at 24 hr. The concentration of In-111-oxine leukocytes in all three types of inflammatory lesion was invariably much higher than that of Ga-67 injected simultaneously. For bacterial abscesses, the mean abscess-to-muscle concentration ratio was 3,000 for labeled leukocytes and 72 for Ga-67. Aqueous buffered In-111 oxine sulfate solution appeared better for labeling leukocytes than In-111 oxine in ethanol. When In-111 oxine was not incubated with leukocytes before injection, or if the cells were poorly labeled or damaged, the abscess localization was often inferior to that of gallium. Localization of In-111 chloride also appeared inferior to that of gallium. No significant difference in distribution in the major organs or inflammatory lesions was demonstrable between labeled suspensions of "pure"neutrophils harvested by elutriation and "mixed"cell suspensions of leukocytes after erythrocyte sedimentation with hydroxyethyl starch. For both types of leukocyte suspension labeled with In-111 oxine, the average recovery of cell-bound activity in the circulating blood at 4 hr was 32% of the administered activity, inferior to that of DFP-32. It is concluded, therefore, that In-111 oxine is a more effective agent than Ga-67 for the detection of acute focal inflammatory lesions if leukocytes are properly labeled, but current techniques are unsatisfactory for the study of neutrophil kinetics.

Topics: Abscess; Animals; Arthritis; Dogs; Female; Gallium Radioisotopes; Hydroxyquinolines; Indium; Inflammation; Isotope Labeling; Leukocytes; Male; Oxyquinoline; Radioisotopes; Radionuclide Imaging; Tissue Distribution