[D-penicillamine: mechanism of cellular action and induced autoimmune diseases]

The fall in the IgM rheumatoid factors under treatment is not sufficient to explain the effectiveness of D-penicillamine in rheumatoid arthritis. The mechanism of action of D-penicillamine is still poorly elucidated. In vitro, in the presence of copper ions, D-penicillamine inhibits the lymphoblastic transformation induced by polyclonal mitogens; it decreases the production of immunoglobulins by lymphocytes stimulated by the Pokeweed mitogen. This inhibitory action is exerced on the helper T lymphocytes via the production of hydrogen peroxide (H2O2). Monocytes are capable of blocking the inhibitory action of D-penicillamine. The mechanism of the auto-immune complications induced by D-penicillamine is controversial. Two theories have been proposed:--a modification of the auto-antigens due to the presence of the highly reactive thiol group;--an interference with the lymphoid cells involved in suppressor or effector lymphocyte cellular co-operation. These auto-immune complications can be classified into two groups: organ-specific diseases such as myasthenia, polymyositis, thyroiditis, and non organ-specific diseases such as Sjögren's syndrome and lupus. The suspension of D-penicillamine generally leads to the resolution of the symptoms, but corticosteroid and immunosuppressant treatment is sometimes required.