Prostaglandins and cell–mediated immunity: The role of prostaglandin E₁ in the induction of host–versus-graft and graft–versus–host reactions in mice

Based on studies in lymphocyte cultures it has been suggested that endogenous prostaglandins (PG), especially those of the E series (PGE), suppress cell-mediated immune reactions during their induction phase. We have tested this theory in experimental animals using local host–versus–graft (HVG) and graft–versus–host (GVH) reactions in mice. These reactions were suppressed in a dose–dependent manner by treatment of the animals with PGE₁. If, however, endogenous PGE was neutralized through treatment of the animals with immune sera directed against PGE (APSE₁) then inhibition of the development of HVG and GVH reactions was seen. This inhibition could be abrogated in “add back” experiments by treatment of the animals with PGE₁. We suggest that the action of PGE₁ during the induction phase of CMI responses is governed by a bell–shaped dose–response curve with a response–enhancing effect at low PGE 1 and a suppressive effect at high PGE₁ concentrations. APSE 1 has proved to be very effective in inhibiting responses, and thus treatment with anti–PG antibodies may not only represent a valuable tool for the study of the role of PG in immunoregulation, but may become useful in therapeutic interventions with the immune system—e.g., after bone marrow transplantation.