Activation of the hypothalamic-pituitary–adrenal gland (HPA) axis can modulate the immune system. Cytokines and neuropeptide Y (NPY) are potent regulators of the HPA axis and are both produced by the adrenal medulla. The cytokine interleukin-1β (IL-1β) belongs to the interleukin-1 family along with interleukin-1α and the interleukin receptor antagonist (IL-1ra). The aim of the present study was to determine the interaction between NPY and IL-1β in catecholamine (norepinephrine, NE and epinephrine, EP) release from mouse chromaffin cells in culture. We found that IL-1β increased the constitutive release of NPY, NE and EP from mouse chromaffin cells. This IL-1β stimulatory effect was blocked by IL-1ra. The immunoneutralization of NPY and the use of the NPY Y1 receptor antagonist (BIBP 3226) inhibited the stimulatory effect of IL-1β on catecholamine release from these cells. The present work shows that IL-1β induces catecholamine release, and in turn this peptide will induce an additional increase in catecholamine release acting through the Y1 receptor. This work suggests that NPY is involved in the regulatory loop between the immune and the adrenal system in some pathophysiological conditions where plasmatic IL-1β increases, like in sepsis, rheumatoid arthritis, stress or hypertension.