D-penicillamine in vivo enhances lymphocyte DNA synthesis: role of macrophages.

Administration of D-penicillamine (50 mg/kg/day orally) for 4 days increased the uptake of 3H-thymidine (3H-TdR) in unstimulated and concanavalin-A-stimulated unseparated lymph node and spleen cells from Lewis rats. Increased 3H-TdR incorporation was also found in cultures depleted of adherent cells. D-Penicillamine treatment did not increase the incorporation of 3H-TdR in lymph node and spleen cells from rats concomitantly treated with the selective macrophage toxin silica. In contrast, treatment with D-penicillamine during the last 4 days of silica treatment sometimes resulted in a marked decrease in 3H-TdR incorporation. It is suggested that D-penicillamine treatment in vivo is able to enhance the responsiveness of the lymphocytes, dependent on the presence of functionally intact macrophages. The increased response vanished after 2-3 weeks, even with continuous administration of D-penicillamine.