Inhibition of immune functions by antiviral drugs.

Abstract

Immune functions were evaluated in vitro for PBMC isolated from healthy donors and cultured with the antiviral agents, 3'-azido-3'-deoxythymidine (AZT), ribavirin, ganciclovir, 2'3'-dideoxyinosine (ddl), or acyclovir. To identify methods for assessing the effects of antiviral drugs on immune cells, the PBMC response to mitogens, Con A, or phytohemagglutinin was evaluated from measurements of [Hjthymidine and 11[Cleucine incorporation, cell growth, cellular RNA, DNA, and protein levels, and the PBMC proliferative cycle (i.e., progression from GO --G1 --S -G2 + M).At clinically relevant concentrations, AZT, ribavirin, or ganciclovir diminished PBMC responsiveness to mitogen. The numbers of proliferating cells in G1, S., and G2 + M phases of the cell cycle, DNA content, and VHjthymidine uptake were decreased in cultures treated with AZT, ribavirin, or ganciclovir. AZT or ribavirin but not ganciclovir reduced RNA and protein in the cultures and inhibited cell growth. Whereas AZT, ribavirin, or ganciclovir were antiproliferative, ddI or acyclovir had little, if any, effect on PBMC mitogenesis. The inhibitory effects of antivirals on immune cells may contribute to the immune deterioration observed in patients following prolonged use of the drugs. (J. Clin.

The antiviral compound ribavirin modulates the T helper (Th) 1/Th2 subset balance in hepatitis B and C virus-specific immune responses.

“…Corroborating previous observations (Heagy et al, 1991), we noted that ribavirin inhibited PHA-induced proliferation of both human and murine T cells at 1 µM (Fig. 2 a, and data not shown).…”

“…Heagy et al (1991) showed that ribavirin inhibits proliferation of polyclonally activated human PBMCs in a dose-dependent fashion. Ribavirin has also been shown to have inhibitory effects on cytokine production by RSVinfected epithelium (Mastronarde et al, 1996), and on the production of IL-6 in RSV-infected pulmonary epithelial cells (Jiang et al, 1998).…”

“…Ribavirin has profound anti-proliferative effect on human peripheral blood mononuclear cells (PBMCs) in vitro : doses ranging from 1 to 10 µM are effective in inhibiting mitogeninduced proliferation (Heagy et al, 1991). This anti-proliferative effect of ribavirin may result from depletion of GTP pools, which are essential for proliferating T cells (Fairbanks et al, 1995).…”

Pilot study of the combination of interferon alfa and ribavirin as therapy of recurrent hepatitis C after liver transplantation

“…21 For those four patients who tolerated the full dose of graft survival in combination with immunosuppressive therapy. [26][27] ribavirin, ALT fell to normal with an improvement in liver histology; serum HCV-RNA, however, remained positive in The most frequently reported side effect of ribavirin has been a dose-related hemolytic anemia. The mechanism of the all patients.…”

AZT inhibits the transmission of human T cell leukaemia/lymphoma virus type I to adult peripheral blood mononuclear cells in vitro.

“…Different concentrations of AZT were assessed for antiviral activity, as well as for effects on cell proliferation and growth. Furthermore, since AZT can modulate some immune functions (Heagy et al, 1991), we investigated the interference of AZT with the expression of some activation markers on cells exposed to HTLV-I.…”