Steroidal antiinflammatory drugs as inhibitors of phospholipase A2

It would seem that steroidal antiinflammatory drugs can block the prostaglandin endoperoxide releasing activity of a wide variety of stimuli. This seems to be due to an inhibition of the release of the fatty acid substrate since the effect is easily reversed by the addition of substrate. The effect of steroids on phospholipase A2 activity in lungs was investigated and it was found that these drugs inhibited the enzyme activity in a time-dependent reversible fashion and that they will block the effect of stimuli such as RCS-RF (bradykinin being an exception). The steroids do not appear to inhibit the phospholipase directly since they do not work in cell-free homogenates. It is too early to say whether or not the antiinflammatory activity of steroids depends on the actions. Many important experiments remain to be done, for example: what exactly is the nature of the phospholipase activation process? Which particular step are the steroids inhibiting? Why do they not work against bradykinin induced stimulation? We hope that in the not too distant future we shall be able to supply the answers to some of these questions.