Selective neutralization of prostaglandin E(2) blocks inflammation, hyperalgesia, and interleukin 6 production in vivo

The role of prostaglandin E(2) (PGE(2)) in the development of inflammatory symptoms and cytokine production was evaluated in vivo using a neutralizing anti-PGE(2) monoclonal antibody 2B5. In carrageenan-induced paw inflammation, pretreatment of rats with 2B5 substantially prevented the development of tissue edema and hyperalgesia in affected paws. The antibody was shown to bind the majority of PGE(2) produced at the inflammatory site, in adjuvant-induced arthritis, the therapeutic administration of 2B5 to arthritic rats substantially reversed edema in affected paws. Anti-PGE(2) treatment also reduced paw levels of IL-6 RNA and serum IL-6 protein without modifying turner necrosis factor RNA levels in the same tissue. In each model, the antiinflammatory efficacy of 2B5 was indistinguishable from that of the nonsteroidal antiinflammatory drug indomethacin, which blocked the production of all PGs. These results indicate that PGE(2) plays a major role in tissue edema, hyperalgesia, and IL-6 production at sites of inflammation, and they suggest that selective pharmacologic modulation of PGE(2) synthesis or activity may provide a useful means of mitigating the symptoms of inflammatory disease.