Role of the blood coagulation system in arthritis and endotoxin induced inflammatory reactions in 6-sulfanilomidoindazole medicated rats

Oral administration of 6-Sulfanilamidoindazole (6-SAI) to aged rats regularly induces an acute, self-limiting arthritis and periarthritis which is confined to the ankles an paws. Sulfonamide feedings resulted in hyperfibriongenmia which preceeded the onset of arthritis by several days. Increases in plasma fibrinogen concentration were associated with increases in serum beta globulin and total globulin concentrations and decreases in serum albumin concentration without changes in total protein concentration. Prolongation of the dilute blood clot lysis time, appearance of heparin precipitable fibrinogen and elevations in serum fibrin degradation products and complement titers were noted in animals with arthritis. Administration of 6-SAI did not result in changes in the whole blood glass and plastic tube clotting times and was not associated with changes in plasma transferrin concentration as determined by the total iron binding capacity. Sulfonamide administration to young rats did not produce arthritis and did not induce increases in plasma fibrinogen concentration. Treatment of 6-SAI medicated rates with large doses of heparin or Warfarin suppressed or inhibited arthritis without suppressing increases in plasma fibrinogen concentration. Concomitant administration of Warfarin and phytonadione resulted in arthritis. 6-ASI induced hyperfibrinogenemia was associated with increased urinary output with out changes in blood volume, plasma volume, red cell volume or blood pH. Elevation in plasma fibrinogen concentration increased blood viscosity but did not increase the erythrocyte sedimentation rate. Induction of severe anemia with phenylhydrazine hydrochloride also suppressed fibrinogen synthesis, reduced blood viscosity and inhibited arthritis in sulfonamide medicated animals. Two consecutive daily administrations of 6-SAI rarely induced arthritis. Tow administration of 6-SAI followed in 24 hours by a single intravenous injection of endotoxin reqularly induced arthritis within 1 or 2 days after endotoxin challenge which was initially characterized by edema and nononuclear cll infiltration of the subsynovial and nononuclear cell tissue and hypertrophyp, hyperplasia and desquamation of the synovial lining cells inot the joint spaces. Lesions in animals sacrificed 5 days following endotoxin challenge were characterized by fibroplasias and granulation tissue formation in the subcutaneous, subsynovial and periarticular tissues. The inflammatory lesions in animals receiving 6-SAI and endotoxin were similar histologically to those seen in animals receiving larger numbers of oral 6-SAI administratons.