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Effects of D-penicillamine on mononuclear cells in vitro
J L Riestra1, M Harth, A Rodriguez
1Rheumatology Section, Hospital Ntra.Sra. de Covadonga Asturias, Spain.
Abstract:
D-penicillamine (D-pen) inhibited pokeweed mitogen-induced plaque-forming cell (PFC) response in a dose-dependent manner. This inhibition was irreversible as preincubation for a few hours with the drug followed by washes still caused suppression of the PFC response. Pretreatment of the different mononuclear cell populations with D-pen for short periods (2-24 h) showed that both macrophages (Mo) and B lymphocytes were affected by the drug. By contrast T cells were resistant. Mo appears to be more susceptible to D-pen than B cells, and in the case of drug-treated Mo, the response was restored completely with the addition of 20% fresh Mo. Our results show that D-pen, without exogenous Cu2+, inhibits the polyclonal immunoglobulin secretion by human mononuclear cells in vitro due to a strong effect on both Mo and B cells. This may explain the decrease in serum immunoglobulin levels seen in patients with rheumatoid arthritis undergoing this therapy.
Insights
D-penicillamine (D-pen) suppresses immune cell function, particularly macrophages and B cells, inhibiting immunoglobulin production. This effect is irreversible and may explain reduced immunoglobulin levels in rheumatoid arthritis patients treated with D-pen.
Area of Science:
- Immunology
- Pharmacology
Background:
- D-penicillamine (D-pen) is a chelating agent used in treating rheumatoid arthritis.
- The drug's impact on immune cell function, particularly immunoglobulin production, requires further elucidation.
Purpose of the Study:
- To investigate the in vitro effects of D-penicillamine on human mononuclear cells and immunoglobulin secretion.
- To determine which immune cell populations are most affected by D-penicillamine.
Main Methods:
- Incubation of human mononuclear cells with varying doses of D-penicillamine.
- Assessment of pokeweed mitogen-induced plaque-forming cell (PFC) response.
- Differential cell population analysis (macrophages, B cells, T cells) following D-penicillamine exposure.
Main Results:
- D-penicillamine inhibited the PFC response in a dose-dependent and irreversible manner.
- Macrophages and B lymphocytes were susceptible to D-penicillamine, while T cells were resistant.
- D-penicillamine significantly affected polyclonal immunoglobulin secretion by inhibiting both macrophages and B cells.
Conclusions:
- D-penicillamine inhibits immunoglobulin secretion in vitro by affecting macrophages and B cells.
- The drug's mechanism involves direct effects on these immune cells, independent of exogenous copper.
- These findings provide a potential explanation for decreased serum immunoglobulin levels observed in rheumatoid arthritis patients treated with D-penicillamine.