Study of psoriatic epidermal cell kinetics and cell death after oral methotrexate

Epidermal cell proliferation in psoriasis was studied after oral methotrexate using tritiated uridine. Psoriatic enteropathy has in the past been reported to reduce the absorption of methotrexate administered orally but this study showed that the onset of inhibition of mitosis and DNA synthesis occurred at the same time as after intramuscular administration of the drug. The cell kinetic data indicate that cells were blocked at the G1/S interface, and the kinetics of inhibition are discussed in terms of their implications for the mode of action of methotrexate in psoriasis. Considerable numbers of dead cells were seen in the epidermis from 6 to 24 h after oral methotrexate. The mode of action of methotrexate in psoriasis is currently unknown but whatever other actions it may have, any global hypothesis of its action will have to incorporate a flux to epidermal cell death.