Immunomodulatory effects of indomethacin and prostaglandin E-2 on primary and secondary antibody response in growing layer hens

Effects of prostaglandin E-2 (PGE(2)) and indomethacin, an inhibitor of PGE (2) oxygenase, on primary and secondary antibody (Ab) responses to Mycobact erium butyricum protein or keyhole limpet hemocyanin (KLH) were studied in growing layer hens. Immunizations at 35 and 70 d of age were accompanied by immunomodulating treatments with PGE(2), indomethacin, or PBS. In addition , we studied effects of various doses of indomethacin and PGE(2) on mitogen -induced T-cell proliferation in vitro. Secondary Ab responses to KLH were enhanced by administration of indomethacin at secondary immunization and, t o a lesser extent, by PGE(2) administration at secondary immunization. Prim ary Ab responses to M. butyricum tended to decrease by administration of ei ther PGE(2) or indomethacin. Secondary Ab responses to M. butyricum were af fected by administration of both PGE(2) and indomethacin at primary immuniz ation. Prostaglandin E-2 increased phytohemagglutinin (PHA)-induced lymphoc yte proliferation. Indomethacin decreased Concanavalin A (ConA)- and PHA-in duced lymphocyte proliferation. The net effect of indomethacin on the Ab re sponse could not be explained by inhibition of PGE(2) oxygenase only. Our d ata rather suggest an inhibition by indomethacin of other immunosuppressing factors derived from arachidonic acid. We concluded that polyunsaturated f atty acid-derived products might especially affect secondary antibody respo nsiveness. This finding may depend on inhibition or enhancement of T-cell r esponsiveness. Consequently, immunomodulation by dietary polyunsaturated fa tty acids may have profound effects at secondary rather than at primary exp osure to pathogens.