Abstract-Effects of D-penicillamine-L-cysteine disulfide (P-C) on some immunological parameters were examined in normal and immunity-impaired mice and rats. P-C enhanced the DNA synthesis in concanavalin A-stimulated mouse spleen cell cultures in vitro. In vivo, administration of P-C produced either enhancement or depression of plaque forming cell (PFC) response and delayed type hypersensitivity (DTH) to sheep red blood cells (SRBC) in low responder mice to SRBC, depending on the dose of P-C. P-C restored the impaired PFC response in hydrocortisone-pretreated mice. The enhancing effect of P-C was not shown in high responder mice to SRBC, but an in hibiting effect was observed. P-C inhibited the suppressor cell induction on PFC response in mice immunized with a supraoptimum dose of antigen. In adjuvant arthritic rats, P-C induced severe arthritis by eliminating the suppressor cells regulating this disease process. The relevance of these findings and mode of action of D-penicillamine in rheumatoid arthritis is discussed.

Experiments were performed in order to ascertain the action of D-penicillamine (PA) on adjuvant arthritis (AA) in rats and to develop a quantitative evaluation method for PA-like drugs, using Lewis, SD, and Wistar rats. Rats were inoculated in the tail with 0.6 mg of Mycobacterium butyricum suspended in 0.1 ml of liquid paraffin. PA apparently induced enhancement of arthritis only in Lewis rats with a good reproducibility. The enhancing effect of PA was seen when it was administered during the period from day -7 to day -1, from day 0 to day 6, or from day 14 to day 20. In control group of Lewis and Wistar rats, adjuvant caused a rapid increase in the cell number of lymph nodes just after the inoculation, and also a marked increase in spleen cells coinciding with the development of arthritis. In PA-treated Lewis rats, the cell numbers of lymph nodes and spleen significantly surpassed those of control rats. However, PA induced no difference from control in Wistar rats, which were not sensitive to PA treatment during the course of arthritis. These results indicate that AA in Lewis rats is a good model for evaluating the activities of PA-like drugs and that PA may affect lymphocytes in lymph nodes and spleen and induce severer arthritis in Lewis rats.

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