REDUCED TOXOPLASMASTATIC ACTIVITY OF MONOCYTES AND MONOCYTE-DERIVED MACROPHAGES FROM AIDS PATIENTS IS MEDIATED VIA PROSTAGLANDIN E(2)

Objective: To establish the role of prostaglandin E(2) (PGE(2)) formed and released by monocytes and monocyte-derived macrophages (MDM) in t he reduced toxoplasmastatic activity of these cells. Design: Determina tion of PGE(2) levels in the serum of AIDS patients, the release of PG E(2) by monocytes and MDM from AIDS patients, the toxoplasmastatic act ivity of these cells and the effect of indomethacin, an inhibitor of P GE(2) synthesis, on this cell function. Setting: Laboratory of Cellula r Immunology of the Department of Infectious Diseases, University Hosp ital, Leiden. Participants: Twenty-six AIDS patients. Healthy blood do nors served as controls. Results: The concentration of PGE(2) in the s erum from AIDS patients was significantly higher compared with serum f rom controls. Non-stimulated monocytes and lipopolysaccharide-stimulat ed monocytes and MDM from AIDS patients released significantly more PG E(2) than corresponding cells from the controls. The proliferation of Toxoplasma gondii in monocytes and MDM from AIDS patients was signific antly higher than in the respective cells from controls. Preincubation of these cells with indomethacin resulted in a decreased proliferatio n of T. gondii in non-activated monocytes and MDM and in interferon-ga mma-activated MDM from AIDS patients. Preincubation of monocytes from healthy donors with PGE(2) resulted in a dose-dependent increase of To xoplasma proliferation which confirms that PGE(2) can reduce the toxop lasmastatic activity of monocytes. Conclusion: PGE(2) is involved in t he reduced toxoplasmastatic activity of monocytes and MDM from AIDS pa tients.