THE ROLE OF SULFHYDRYL GROUPS IN THREE MODELS OF INFLAMMATORY DISEASE

¹ Research Department, Pharmaceutical Division, CIBA-GEIGY Corporation, Ardsley, New York

The role of sulfhydryl (SH) groups in the etiology and therapy of acute and chronic inflammation has been studied in three different rat models: carrageenin-induced paw edema, the croton oil-induced granuloma pouch and the adjuvant-induced polyarthritis. Carrageenin edema was inhibited by indomethacin but not by locally or systemically injected thiols. However, subplantar injection of the SH-binding reagent, N-ethylmaleimide, produced a profound edema which was inhibited by cysteine but by indomethacin. Thus there are both thiol-dependent and independent types of edema. Injection of N-ethylmaleimide into granuloma pouches inhibited exudation. Cysteine reversed this effeet, which suggests that the protein synthesis necessary for exudative granuloma formation is thiol-dependent. Adjuvant injection in rats was followed by a depression of the serum sulfhydryl-disulfide (SH-SS) interchange reaction and the appearance of an abnormal serum -2 glycoprotein, well before the onset of frank arthritis. Tissue (paw) SH levels showed no change. Anti-inflammatory compounds, but not SH donors, restored to normal the impaired serum SH-SS interchange reactions, inhibited the rise in abnormal protein level and suppressed arthritic symptoms. The depressed SH-SS interchange reaction thus appears to be a consequece of, rather than an etiological factor in adjuvant disease. Thus, thiols may be either pro- or anti-inflammatory or have no effect, depending entirely on the model selected for study.