Dermal Connective Tissue Permeability in Rheumatoid Arthritics

Abstract

Dermal connective tissue permeability was studied in vivo in humans by 1 method, and in rats by 2 methods. One method measured the rate of diffusion of intradermally injected Evans blue solution and the other the rate of flow of subdermal saline infusion under constant hydrostatic pressure. The studies on human subjects showed that in patients afflicted with rheumatoid arthritis the spread of intradermally injected dye solution is much greater than in non-arthritic patients and healthy subjects. A variation with age was noted. Some compounds used in the treatment of rheumatoid arthritis were previously inhibited the oxidative-reductive depolymerization of hyaluronic acid in vitro. The oral administration of sodium diethyldithiocarbamate, thiourea, cysteine, and ethanol, substances found to be strong inhibitors in the in vitro reaction, inhibited the permeability of the skin in rats. Sodium diethyldithiocarbamate was the most active; thiourea, sodium salicylate, and cysteine at high concentration also had marked inhibitory effects. These findings indicate a strong parallelism between the in vitro and in vivo reactions. However, among the anti-rheumatic drugs studied, pencillamine and prednisone administered for 3 weeks did not modify the "normal" permeability of the skin in rats, although prednisone had a marked short-term effect. The results in humans and animals suggest that the state of polymerization of hyaluronic acid may be the principal regulator of permeability phenomena in the ground substance.