Azathioprine's inhibitory effect on prostaglandin E₂ production is not via cyclooxygenase inhibition

Azathioprine, a widely used antimetabolite, is also known for its anti-inflammatory action in rheumatic disorders and in uveitis, an inflammation of the eye, both of which are associated with increased production of prostaglandin E₂. Recently we demonstrated that prostaglandin E₂ production by rabbit retina/ choroid was inhibited by azathioprine and suggested that this inhibitory effect may underlie the drug's antiinflammatory action. In the present study we showed that azathioprine's inhibition of prostaglandin E₂ synthesis by the rat retina/choroid was reversed by addition of arachidonic acid, indicating that inhibition occurred through lack of availability of arachidonic acid, similar to the mechanism underlying the inhibitory effect of the steroidal anti-inflammatory drugs on prostaglandin E₂. This study rules out the possibility that azathioprine's suppressive activity is via inhibition of the cyclooxygenase pathway.