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.

Effect of IFN-gamma on the proliferation of Toxoplasma gondii in monocytes and monocyte-derived macrophages from AIDS patients.

This study was undertaken to determine whether the activity of monocytes and monocyte-derived macrophages (MDM) from acquired immune deficiency syndrome (AIDS) patients against Toxoplasma gondii is altered and whether this activity can be modulated by recombinant interferon-gamma (rIFN-gamma). Untreated and rIFN-gamma-treated monocytes or MDM from AIDS patients and from healthy controls were infected with T. gondii and the proliferation of these protozoa was determined. The H2O2 release by monocytes from AIDS patients and healthy controls was measured upon stimulation with phorbol myristate acetate (PMA) and formyl methionyl leucyl phenylalanine (FMLP). Monocytes from AIDS patients exhibited significantly lower toxoplasmastic activity compared to monocytes from healthy controls. The H2O2 release by monocytes from AIDS patients was also diminished. Incubation of monocytes from AIDS patients with rIFN-gamma for 2 days, but not 1 day, restored their toxoplasmastatic activity. The rate of proliferation of T. gondii was higher in MDM from AIDS patients than in MDM from healthy controls. Treatment of MDM from AIDS patients with rIFN-gamma for 1, 2 or 3 days resulted in partial inhibition of the proliferation of T. gondii. Collectively, these results demonstrate that the reduced toxoplasmastatic activity of monocytes and MDM from AIDS patients can be enhanced by in vitro treatment with rIFN-gamma, which supports the clinical use of rIFN-gamma for the treatment of opportunistic infections in these patients.

Prevention of nosocomial spread of multidrug-resistant tubercle bacilli.

Outbreaks of multidrug-resistant Mycobacterium tuberculosis (multidrug-resistant tuberculosis; MDR-TB) have recently been reported in hospitals in the United States. Rapid spread of these bacilli and a high mortality among immunocompromised patients, i.e. HIV-infected individuals and AIDS patients, were observed. Factors that play a role in these outbreaks and the prevention of MDR-TB are discussed in this article. Awareness of a possible M. tuberculosis infection and the early introduction of measures to reduce the spread of these micro-organisms are steps that can prevent a nosocomial outbreak. The use of more rapid methods for culturing mycobacteria and determining their sensitivity to antimicrobial drugs can accelerate the diagnostic process and the recognition of multiresistance. In view of the poor results of treatment of MDR-TB, prevention should be the first requirement.

Sjögren's syndrome complicated by cryoglobulinaemia and acute renal failure.

A patient is described with Sjögren's syndrome and an IgM-kappa gammopathy. With time cryoglobulins, the cause of acute renal failure, could be detected. The kidney biopsy showed a proliferative glomerulonephritis as is frequently seen with mixed cryoglobulinaemia. Plasmapheresis and immunosuppression resulted in long-term improvement of kidney function. The differential diagnosis of acute renal failure of glomerular origin in a patient with Sjögren's syndrome is discussed. This case report illustrates once more the consequences of monoclonal B-cell lymphocyte activation in Sjögren's syndrome.