Reduced toxoplasmastatic activity of monocytes and monocyte-derived macrophages from AIDS patients is mediated via prostaglandin E2.

OBJECTIVE

To establish the role of prostaglandin E2 (PGE2) formed and released by monocytes and monocyte-derived macrophages (MDM) in the reduced toxoplasmastatic activity of these cells.

DESIGN

Determination of PGE2 levels in the serum of AIDS patients, the release of PGE2 by monocytes and MDM from AIDS patients, the toxoplasmastatic activity of these cells and the effect of indomethacin, an inhibitor of PGE2 synthesis, on this cell function.

SETTING

Laboratory of Cellular Immunology of the Department of Infectious Diseases, University Hospital, Leiden.

PARTICIPANTS

Twenty-six AIDS patients. Healthy blood donors served as controls.

RESULTS

The concentration of PGE2 in the serum from AIDS patients was significantly higher compared with serum from controls. Non-stimulated monocytes and lipopolysaccharide-stimulated monocytes and MDM from AIDS patients released significantly more PGE2 than corresponding cells from the controls. The proliferation of Toxoplasma gondii in monocytes and MDM from AIDS patients was significantly higher than in the respective cells from controls. Preincubation of these cells with indomethacin resulted in a decreased proliferation of T. gondii in non-activated monocytes and MDM and in interferon-gamma-activated MDM from AIDS patients. Preincubation of monocytes from healthy donors with PGE2 resulted in a dose-dependent increase of Toxoplasma proliferation which confirms that PGE2 can reduce the toxoplasmastatic activity of monocytes.

CONCLUSION

PGE2 is involved in the reduced toxoplasmastatic activity of monocytes and MDM from AIDS patients.