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Studies of D-penicillamine (3): immunomodulating effects of D-penicillamine
Abstract:
D-penicillamine (D-PA) has beneficial therapeutic effects for patients with rheumatoid arthritis but no convincing explanation has been offered for the mode of action. Experiments reported here were designed to gain an insight into the related mechanisms. Wistar rats were inoculated with various doses of Mycobacterium tuberculosis to induce adjuvant arthritis, and on the 21st day, the lesions of paws and ears were graded according to the extent of the erythema and swelling. Rats given D-PA simultaneously with the inoculation of M. tuberculosis developed a more severe arthritis than that seen in the control group, when they were inoculated with low doses of M. tuberculosis. To investigate the effect of D-PA on hemolytic plaque forming cells (PFC) in the spleen, BDF1 mice were immunized with various doses of sheep red blood cells (SRBC) and D-PA was injected in various doses and at various times. D-PA produced either enhancement or depression of the number of PFC, depending on the dose of antigenic stimulus of SRBC. Furthermore, D-PA slightly enhanced the concanavalin A-induced blastogenesis of the spleen cells in vitro, at a concentration of 1-50 microM, but at concentrations of 500 microM, inhibition was evident. These results indicate that D-PA may act as an immunomodulating agent.
Insights
D-penicillamine (D-PA) may worsen arthritis in rats but can enhance or suppress immune responses in mice, suggesting it acts as an immunomodulating agent. Further research is needed to understand its complex effects.
Area of Science:
- Immunology
- Pharmacology
- Rheumatology
Background:
- D-penicillamine (D-PA) is used for rheumatoid arthritis, but its mechanism of action is unclear.
- Understanding D-PA's effects on the immune system is crucial for explaining its therapeutic benefits.
Purpose of the Study:
- To investigate the immunomodulatory mechanisms of D-penicillamine (D-PA).
- To explore D-PA's impact on immune responses in animal models.
Main Methods:
- Adjuvant arthritis was induced in Wistar rats using Mycobacterium tuberculosis.
- Hemolytic plaque-forming cell (PFC) assays and concanavalin A-induced blastogenesis were performed in BDF1 mice.
Main Results:
- D-PA exacerbated arthritis in rats at low doses of M. tuberculosis.
- D-PA modulated PFC responses in mice, with effects varying based on antigen dose.
- D-PA showed dose-dependent effects on spleen cell blastogenesis in vitro, enhancing at low concentrations and inhibiting at high concentrations.
Conclusions:
- D-penicillamine (D-PA) exhibits immunomodulatory properties.
- D-PA's complex effects on immune responses may explain its varied therapeutic outcomes.