Effects of drugs on different types of synovial inflammation in the rabbit.

Inflammatory joint diseases in man differ markedly in their response to anti-inflammatory agents. Perhaps the best known example is the dramatic effect of salicylates in acute rheumatic fever in contrast to their minimal value in acute juvenile rheumatoid arthritis. Phenylbutazone is quite helpful in treating ankylosing spondylitis, but is of little value in peripheral rheumatoid arthritis. In the last few years, our laboratory has used the cellular exudate in rabbit knee joints as an index of certain types of inflammatory reactions. Injection of foreign proteins into the suprapatellar bursae of non-immunized rabbits leads to granulocytic exudation by some unknown recognition of foreigness; the amount of exudation is roughly proportionate to the degree of foreigness and to the antigenicity of the protein.' Histologically, the synovial lining of rabbits injected with foreign protein shows little vascular change and no deep cellular reaction. In pre-immunized rabbits, injections of foreign protein cause an Arthus-type reaction with vascular dilatation and polymorphonuclear reaction in the deeper tissues of the synovium, and markedly enhanced migration of inflammatory cells into the synovial cavity.'2 Another interesting inflammatory agent is bacterial endotoxin. In extremely small amounts, it produces an intense intraarticular exudate without very striking histologic changes in the synovial tissues.3"' These three types of synovial inflammatory reactions-foreign protein in normal rabbits and in pre-immunized rabbits, and bacterial endotoxin in normal rabbits-have been produced, and the effect of certain anti-inflammatory drugs assayed in each of the model systems. The drugs (salicylates, corticosteroids, chloroquine phosphate, and phenylbutazone) were used in dosages that have been shown to decrease the permeability of rabbit synovial membrane to a macromolecular dye.5