Interleukin-8 is a paracrine inducer of fibroblast growth factor 2, a stromal and epithelial growth factor in benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is an extremely common disease of older men in which there is benign overgrowth of the prostatic transition zone, l eading to obstruction of urine outflow. Fibroblast growth factor (FGF) 2, a potent growth factor for prostatic stromal and epithelial cells, is increa sed twofold in BPH and its concentration is correlated with stromal prolife ration in this condition, immunohistochemistry of normal and hyperplastic p rostate revealed that FGF2-expressing stromal cells were present in higher numbers near the epithelial acini, implying that epithelial cells may expre ss a factor that induces FGF2 expression by stromal cells. Conditioned medi um from primary cultures of prostatic epithelial cells was capable of induc ing increased expression of FGF2 by primary stromal cultures. Blocking expe riments with neutralizing anti-interleukin (IL)-8 antibodies and pretreatme nt with lipopolysaccharide, which down-regulates the IL-8 receptor, show th at this inducing activity is because of the presence of IL-8 in the epithel ial-conditioned medium. Analysis of normal prostatic peripheral zone and BP H tissue by enzyme-linked immunosorbent assay reveals that IL-8 is present at increased levels in hyperplastic prostate. Therefore IL-8 produced by pr ostatic epithelial cells can induce FGF2, a potent stromal and epithelial g rowth factor, and In this manner promote the abnormal proliferation of the prostatic transition zone that is critical in the pathogenesis of BPH.