Age and pro-inflammatory cytokine production: wound-healing implications for scar-formation and the timing of genital surgery in boys.

Purpose: Fewer complications occur when hypospadias is repaired early in childhood. We hypothesize that the production of pro-inflammatory cytokines by fibroblasts from neonatal foreskin is decreased compared with fibroblasts from older boys. We believe that these age-related differences may explain the greater risk of complications following repair in older boys.

Materials And Methods: With IRB approval, we collected 15 samples of foreskin from boys undergoing elective circumcision. They were divided into one of three groups: a neonatal group (under 28 days), an intermediate age group (6 months-1 year), and an older age group (7-17-years-olds). Fibroblasts were cultured then incubated for 16 h with serum-free medium containing 0, 0.1, 1 or 10 ng/mL of PDGF. Supernatants were analyzed for production of IL-6 and IL-8 with quantitative ELISA. Fibroblasts had RT-PCR performed for IL-6, IL-8, IL-10, TGF-β1, TGF-β3 and TNF-α.

Results: Fibroblasts from neonatal foreskin produced significantly less IL-6 and IL-8 at baseline and following stimulation with PDGF compared to the intermediate and older age groups (P < 0.01). Real-time PCR revealed greater expression of IL-6, IL-8, TNF-α and TGF-β1 mRNA in the older age groups (P < 0.05).

Conclusions: There is a clear association between age and production of pro-inflammatory cytokines by genitourinary fibroblasts. This relationship exists at baseline and following stimulation with PDGF. The dramatic difference in levels of pro-inflammatory factors may explain the observed age-associated differences in wound scarring and stricture formation following hypospadias repair. Further clinical studies are needed, however, to validate this finding.