In vitroimmunotoxicity of ±2′-deoxy-3′-thiacytidine, a new and-HIV agent

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Abstract
SUMMARY: The present study compares the in vitro effect of (±)-2′-deoxy-3′-lhiacylidine (BCH 189) a new synthetic anti-HIV-l dideoxynucleosidc. with 3′-azido-3′-deoxythymidinc (AZT) on the immune function of lymphocytes from 10 normal and 12 HIV-1+ patients (CDC II and III). The effect of different doses of BCH 189 and AZT was analysed in vitro on: (i) T cell proliferation after stimulation with concanavalin A (Con A) or anti-CD3 MoAb: (ii) B cell proliferation and immunoglobulin production after stimulation with pokeweed mitogen (PWM); (iii) cytokine production (IL-2. IL-6. GM-CSF, tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) from lymphocytes stimulated with anti-CD3 MoAb or phylohucmagglutinin (PHA). BCH 189 inhibited the proliferation of B and T lymphocytes from normal and HIV’ subjects less than AZT: even if lymphocytes from HIV+ (CDC HI) subjects produced higher levels of IL-6 and TNF-α, neither BCH 189 nor AZT molecule interfered with cytokine release. Immunoglobulin production from B lymphocytes was inhibited only by a high concentration (50 μm) of BCH 189 or AZT. These results show that BCH 189 affects lymphocyte proliferation in vitro less then AZT, and support its use in clinical trials in HIV-infected patients.

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