Induction of arthritic processes by synovial fluids of rheumatoid arthritis patients in long-term experiments with mice.

Diluted synovial fluids derived from three patients with rheumatoid arthritis (RA) and applied subcutaneously once as a single dose in Swiss mice caused arthritic processes after a long period of latency (10 months). The arthritis-inducing effect was enhanced by storing the original synovial fluids at 4 degrees C for three months. The effects were followed histologically for at least 18 months. In contrast to the theory that RA is based on immunological processes, these preliminary observations support the finding of other authors that a transmissible agent which is rather slow-acting exists in the synovial fluid of RA patients.

Aetiology of rheumatoid arthritis: an attempt to transmit an infective agent from patients with rheumatoid arthritis to baboons.

Thirty baboons were injected intravenously and intra-articularly with material from the joints of 19 patients with active rheumatoid arthritis or with control material. Fifteen of the 30 animals received synovial fluid cells or synovial membrane cells from 3 patients with seronegative arthritis. Ten animals received pooled cells from a total of 16 cases of seropositive arthritis. Five animals were given nonrheumatoid cells. No signs of arthritis were recognised in the 27 surviving animals during 3 years of observation. No significant biochemical, haematological, or serological changes occurred during this period, and no gross or microscopic evidence of synovial or systemic disease was found post mortem.

Increased incidence of adjuvant arthritis in Wistar rats.

The moderate incidence of arthritis in Wistar rats after inoculation of a suspension of Mycobacterium butyricum in oil increased to nearly 100% by two modifications. Inoculation with 4 week- as compared to 1 week-cultured. M. butyricum raised the incidence from 34 to 63%. Inoculation of this more arthritogenic material into the F1-descendants of M. butyricum sensitive parents raised the incidence of 96%. Also the severity of the arthritis in rats selected in that manner was higher than in non-selected rats. Treatment of arthritic rats of either source with phenylbutazone resulted in a comparable dose-related reduction of the diameters of the hind-limbs. Mating of rats with various degrees of arthritic response showed that sensitivity transmission to the F1-descendants was optimal with the most sensitive parents. Although the exact nature of the transmission has not been defined, the uniform and higher sensitivity of thus selected rats is of great value for quantitative pharmacological studies.

Thermal inactivation and gradient studies of the active agent in rheumatoid arthritis.

Ten day embryonated eggs have been used for testing supernatants of pooled RA synovial tissues for the presence of the RA-active agent. A high thermal resistance of the agent was observed up to 40 min of heating both at 100 and 121 degrees C with complete loss of infectivity only after 60 min at 121 degrees C. The high thermal resistance at 121 degrees C suggested that the active agent does not depend on a double-stranded DNA or RNA. It probably has no protein component and has a minimal number of subunits for replication. The CsC1 ultracentrifugation identified a concentration of high infectivity at densities in the range of 1.440-1.490 g/ml in five experiments.