THE EFFECT OF 1,25-VITAMIN-D3 ON MATURATION OF MONOCYTES FROM HIV-INFECTED PATIENTS VARIES WITH DEGREE OF IMMUNODEFICIENCY

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D-3 (1,25D), has been shown to induce monocyte-to-macrophage maturation in vitro a s well as monocytic differentiation of bone marrow precursors and mono cytic leukaemic cell lines. In this study we assessed whether 1,25D co uld improve the maturation defect we have previously demonstrated in m onocytes from AIDS patients. In vitro growth and maturation of monocyt es from 10 controls, 15 asymptomatic HIV positives (CDC group II or II I) and 13 symptomatic HIV positives (CDC group IV) was examined by ass essing cellular morphology, differentiation, adherence and protein con tent. Cells were cultured for 10 days with or without addition of 1,25 D at a concentration of 100 pg/ml. In addition, patients were monitore d clinically and by immunological parameters and HIV p24 antigen in se rum. The present study showed that addition of 1,25D significantly imp roved the growth and maturation in both patient and control groups. Th ere was a significant negative correlation between response to 1,25D a nd CD4+ lymphocyte count in blood in HIV-infected patients. A greater response to 1,25D was seen in monocytes from patients with advanced im munodeficiency and symptomatic disease than in monocytes from asymptom atic patients. However, in the most advanced cases of HIV infection wi th serious ongoing opportunistic infections the response to 1,25D was very poor, possibly reflecting profound and incorrigible dysfunction o f monocytes.