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Increased synthesis and production of prostaglandin E2 by monocytes from drug addicts with AIDS
E Fernández-Cruz1, E Gelpi, N Longo
1Department of Immunology, Hospital General Gregorio Marañón, Madrid, Spain.
Abstract:
We analysed the production of prostaglandin E2 (PGE2) by monocytes in 11 drug addicts with AIDS and opportunistic infections and in 13 controls. In three patients and six controls we isolated the PGE2 fraction from culture supernatants of purified monocytes (greater than 95%) incubated in medium containing (3H) arachidonic acid, using silicic acid columns. In two of three patients PGE2-fraction values (21.9 and 21.6 pmol/g protein) were significantly higher than controls (10 +/- 4). In eight AIDS patients and seven controls, PGE2 levels were determined by high-performance liquid chromatography and radioimmunoassay (HPLC and RIA). In three out of eight patients PGE2 levels were markedly higher (736, 419 and 208 pg/ml) than the mean + 2 s.d. values from controls (73 +/- 51). We tested the effect of PGE2 on the production of interleukin-2 by normal phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL). There was a significant suppression of interleukin-2 production by PGE2 released from AIDS monocytes. PGE2 may be one of the factors involved in the severe immune dysfunction associated with AIDS.
Insights
Monocytes from individuals with AIDS and opportunistic infections produce significantly higher levels of prostaglandin E2 (PGE2). This elevated PGE2 suppresses interleukin-2 production, contributing to immune dysfunction in AIDS patients.
Area of Science:
- Immunology
- Virology
- Biochemistry
Background:
- Acquired Immunodeficiency Syndrome (AIDS) is characterized by severe immune dysfunction.
- Monocytes play a critical role in immune responses and are affected by HIV infection.
Purpose of the Study:
- To investigate prostaglandin E2 (PGE2) production by monocytes in patients with AIDS and opportunistic infections.
- To determine the effect of monocyte-derived PGE2 on interleukin-2 (IL-2) production by lymphocytes.
Main Methods:
- Purified monocytes from 11 drug addicts with AIDS and 13 controls were cultured with (3H) arachidonic acid.
- Prostaglandin E2 (PGE2) was isolated using silicic acid columns and quantified.
- PGE2 levels were further analyzed using high-performance liquid chromatography and radioimmunoassay (HPLC and RIA).
- The effect of PGE2 on phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) was assessed by measuring IL-2 production.
Main Results:
- Two of three AIDS patients showed significantly higher PGE2 fractions compared to controls.
- Three of eight AIDS patients exhibited markedly elevated PGE2 levels by HPLC and RIA.
- PGE2 released from AIDS monocytes significantly suppressed IL-2 production by normal lymphocytes.
Conclusions:
- Elevated PGE2 production by monocytes is observed in patients with AIDS and opportunistic infections.
- Monocyte-derived PGE2 contributes to the suppression of interleukin-2 (IL-2) production.
- PGE2 is implicated as a factor in the severe immune dysfunction associated with AIDS.