Interleukin-2 increases choline acetyltransferase activity in septal-cell cultures

Interleukin-2 (IL-2) is a potent modulator of in vitro acetylcholine release in hippocampal slices [Hanisch et al. (1993) J. Neurosci., 13:3368]. In order to further investigate the cellular nature of this effect, we used embryonic septal-cell cultures (E17), known to be enriched with the cholinergic phenotype. Septal cells were grown at different plating densities under serum-free conditions. The effect of IL-2 on the expression of the cholinergic phenotype was determined using choline acetyltransferase (ChAT) activity and acetylcholinesterase (AChE) cytochemistry. IL-2 significantly enhanced ChAT activity in 5-day-old cultures (5 days in vitro). The amplitude of increases correlated with plating density. At 5 x 10(5) cells/well, the increase in ChAT activity was 35-55% greater than control values in the presence of 10(-14)-10(-10) M IL-2, whereas at 7.5 x 10(5) cells/well, this increase was substantially lower (20%) and only observed at concentrations between 10(-13)-10(-11) M. At 10(6) cells/well, IL-2 had no effect on ChAT activity. The IL-2-induced increase in ChAT activity was significantly inhibited in the presence of an IL-2 receptor antibody. Moreover, this increase was not dependent upon trophic actions, as the number of AChE-positive cells or their morphological characteristics were not altered by IL-2. Taken together, these results suggest that IL-2 can stimulate, at pM concentrations, ChAT activity by acting via its own receptors expressed by septal neurons.