The IFN-γ response induced by zoledronate and IL-2 in the CD56⁺ subset depends on endogenous IL-1β and TNF-α. (A) CD56⁺ cells (10⁶/mL) were stimulated with zoledronate plus IL-2 in the presence of control (−/−) or neutralizing antibodies against IL-1β or TNF-α. In 3 independent experiments IFN-γ production induced by zoledronate plus IL-2 was strongly inhibited by IL-1β neutralization and to a lesser but still significant extent by neutralization of TNF-α. Asterisks indicate statistical significance between the groups that received control or neutralizing anti–IL-1β or anti–TNF-α antibody according to Student t test for *P < .05, **P < .01. Error bars indicate the SEM from 3 independent experiments. (B) CD56⁺ cells (10⁶/mL) were stimulated with low-dose zoledronate plus IL-2 in the presence or absence of recombinant IL-1β (1 ng/mL), TNF-α (100 U/mL), or a combination of IL-1β and TNF-α. The levels of IFN-γ and IL-6 in day 5 culture supernatants are strongly up-regulated by IL-1β and to a lesser extent by TNF-α. Data are mean values of duplicate cultures from a representative experiment (n = 3).