RESUMEN
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.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/metabolismo , Dinoprostona/biosíntesis , Monocitos/metabolismo , Trastornos Relacionados con Sustancias/metabolismo , Humanos , Infecciones Oportunistas/metabolismo , Tromboxano B2/biosíntesisRESUMEN
We have studied immunological, serological and clinical abnormalities in 264 HIV-positive and HIV-negative drug abusers. Ninety percent of the 264 drug addicts (mean age 26 +/- 0.8 years) were found to have HIV antibodies and there was a significant increase (P less than 0.01) in the frequency of HIV antibody positivity with increasing duration of exposure to parenteral drug abuse. There was a very strong correlation between the progressive decline of the mean T4+ helper/inducer cells and T4+/T8+ ratio, the low response to pokeweed mitogen and the more severe clinical manifestations of HIV infection. Impairment of delayed-type hypersensitivity reaction to recall antigens was only seen in group IV as defined by the Center for Disease Control. Within group IV, anergy was found to be highly associated (83%) in patients with opportunistic infections. All other HIV-positive addicts from groups II and III, as well as HIV-negative addicts had normal in vivo responses to test antigens. We have also analysed in a prospective follow-up lasting 6-24 months, the evolution of HIV infection in a cohort of 50 HIV-antibody-positive drug addicts. Thirty-two percent showed clinical progression and most of the drug addicts that proceeded to full-blown AIDS developed anergy (82%) prior to clinical deterioration with development of opportunistic infections. We conclude, that in seropositive drug addicts a low absolute count of helper/inducer cells (mean +/- s.e. = 243 +/- 48 cells/mm3), a low response to pokeweed mitogen and anergy are predictive markers of progression to AIDS.