Anti-PGE antibodies inhibit in vivo development of cell-mediated immunity.

Abstract

Prostaglandins have been implicated in the regulation of humoral and cell-mediated (CMI) immunity, but little is known about their precise mode of action; published data indicate both enhancing and suppressing activity of these substances1–4. E-type prostaglandins (PGEs) act as extracellular modulators of the function of T lymphocytes5,6 and there may be differences in the sensitivity of different T-cell subpopulations to this modulation7–9. As most studies have used in vitro test systems, it is unknown whether prostaglandins have the same effects in vivo4. We have therefore examined the role of PGEs in CMI in vivo. Prostaglandins are derived from essential fatty acids (EFA) via the cyclooxygenase system, and inhibition of this pathway by aspirin or indomethacin10,11 has been widely used to study prostaglandin effects. However, the usefulness of these substances in vivo is restricted by their toxicity and limitations in their selective action12,13. An alternative is to use anti-prostaglandin antibodies, which antagonize F- and E-type prostaglandins in experimental animals14,15 and prevent PGI2 from inhibiting ADP-induced platelet aggregation16. We report here that anti-PGE antisera significantly suppressed experimental allergic encephalomyelitis (EAE) in rats and prevented the generation of host-versus-graft (HvG) and graft-versus-host (GvH) reactions in mice, suggesting that PGEs are important mediators not only of in vitro induction of CMI responses8,9 but also of the early phase of CMI in vivo.