Neuroendocrine differentiation in prostate cancer has received much attention recently because it has been found to be associated with androgen independence and shortened patient survival in some studies. We have investigated the effect of the cytokines interleukin-1 (IL-1), IL-2, and IL-6 on the expression of the neuroendocrine marker chromogranin A in human prostate cancer cell lines. Chromogranin A was measured by fluorescence-immunoassay, as well as by immunoblotting. We find that IL-1beta and IL-6 increase the cellular content and chromogranin A secretion by LNCaP and DU-145 cells. By contrast, IL-2 decreases the cellular and secreted chromogranin A levels in the two cell lines. Our results suggest that these proinflammatory cytokines can influence neuroendocrine differentiation in prostate cancer and be involved in disease progression.