Proinflammatory cytokines play an essential role in the development and progression of prostate cancer (PCa). Especially interleukine (IL-)6 is involved in the development of aggressive PCa. Peripheral blood mononuclear cells (PBMC) have been reported to interact with cancer cells and subsequently lead to increased production of pro-inflammatory cytokines. However, the role of anti-nflammatory cytokines, such as IL-4 is still largely unexplored in prostate cancer. In the present study, we investigated the effects of IL-4 on PBMC co-cultured with PCa cells. PBMC were co-culured with the PCa cell lines LNCaP and LNCaP-IL6+. To avoid cell-cell contact, cancer and immune cells were separated using cell culture inserts with a 0.4 μm pore size membrane. Cell growth was assessed using the [3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide] (MTT) assay. Cytokine levels were measured using a BD™Cytometric Bead Array. Cell viability of LNCaP cells decreased massively when cells were co-cultured with PBMC. Pre-incubation with IL-4 could partly rescue the observed effect of cell viability of LNCaP cells co-cultured with PBMC. In contrast, cell viability of the LNCaP-IL6+ cell line was not affected when co-cultured with PBMC. IL-4 counteracts the cytotoxic effects of PBMC on hormone-sensitive LNCaP cells and is involved in the immune escape and development of aggressive phenotypes of PCa.