Role of Lymph Nodes in Adjuvant-induced Arthritis in Rats.

The arthritic syndrome induced in rats by an intradermal injection of a fine suspension of dead mycobacteria in liquid paraffin was first described by Stoerk, Bielinski, and Budzilovich (1954) and later studied in detail by Pearson (1956, 1959). The syndrome is characterized by the appearance of inflamed lesions, called secondary lesions, remote from the injection site after a delay of approximately 10 days. The mechanisms involved in the development of secondary lesions are still obscure. There is little evidence to support the idea that an infectious agent is involved (Sharp, Waksman, Pearson, and Madoff, 1961), although Jones and Ward (1963), from their histological studies, consider that this is still a possibility. It is also unlikely that an auto-immune mechanism resulting from tissue damage at the injection site is involved, since Ward and Jones (1962) showed that, whilst the development of secondary lesions was prevented by removing the depot within 2 hours of injecting adjuvant into the tail, removal after this time had no effect. Considerable evidence has been presented which suggests that secondary lesions are the result of a delayed hypersensitivity response to disseminated antigen which is probably derived from the injected tubercle bacilli (Waksman, Pearson, and Sharp, 1960). However, most of this evidence is indirect and little is known about the precise steps involved. Recently, it was shown that a pre-requisite for the development of secondary lesions was the presence of adjuvant in the lymphatic system (Newbould, 1964). Because of the association between lymph nodes and antibody production, regional lymph nodes may play an important role in the development of secondary lesions. Previous attempts to interfere with the development of secondary lesions by removal of the popliteal lymph node draining the injection site in the foot were unsuccessful (Waksman and others, 1960). However, adjuvant injected into the foot pad is disseminated to many nodes (Newbould, 1964). It therefore seemed likely that more lymph nodes would have to be removed before their significance in the development of the syndrome could be assessed. The object of the work reported here was to study the effect of removal of draining lymph nodes on the development of secondary lesions when the nodes were removed at the time of injection of adjuvant and at intervals thereafter.