Immune-associated toxicities induced by in vivo and in vitro exposure to interferon-alpha alone or in combination with nucleoside analogs.

The present studies examine whether immune-associated toxicities develop in rodents exposed to recombinant human interferon-alpha A/D (rHuIFN-alpha) alone or in combination with anti-retroviral nucleoside analogs. Four findings have emerged from these studies: (1) lymphocyte cell number and functional activity are suppressed after subchronic (1, 8 or 10 day) in vivo exposure to therapeutic doses of rHuIFN-alpha; (2) lymphocyte-associated toxicities lessen as in vivo exposure time to rHuIFN-alpha is extended; (3) T-cell-dependent antibody production is decreased after in vitro exposure of both antigen-specific T- and B-cells to rHuIFN-alpha; and (4) in vivo-induced leukocyte toxicities associated with either rHuIFN-alpha or the nucleoside analogs alone do not synergize when the therapies are combined. These data suggest that certain key immune parameters should be monitored carefully in the early stages of IFN-alpha therapy.