When EPA or DHA take the place of AA the result is inhibition of inflammatory processes. The target of pain killing medications is to prevent the action of the enzymes which make cytokines. EPA and DHA use a completely different target. They do not block the enzymes which make the cytokines; instead they replace the fat the cytokines are made from!

Both EPA and DHA compete with AA for conversion to cytokines:
Including frequent fish consumption, or supplementing with fish oil leads to a very substantial increase in the amount of EPA and DHA in cell membranes. When phospholipase A2 searches for a fat it now has a much greater chance of releasing a molecule of EPA or DHA instead of releasing a molecule of AA. With less AA released from the membrane, less cytokines formed from AA will also be produced. The net result is a reduction in inflammation. This is the “competitive effect” of both EPA and DHA on cytokine production.

EPA produces anti-inflammatory cytokines:
When cyclooxygenase or lipoxygenase act upon EPA new cytokines are made. The cytokines produced from EPA are similar in structure to the cytokines produced from AA but they have very different biological effects. Instead of promoting inflammation and pain, the EPA- derived cytokines are anti-inflammatory. They will oppose the action of cytokines which do end up being made from AA.

Due to the concept of competition with AA, DHA is able to benefit inflammation. DHA does not give rise to biologically active cytokines. This suggests that EPA is likely more important to the prevention of inflammation than DHA, although both EPA and DHA have shown benefit to inflammation in human studies.