title: Age and pro-inflammatory cytokine production: wound-healing implications for scar-formation and the timing of genital surgery in boys.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Hospital of the University of Pennsylvania, 3400 Spruce Street, Department of Surgery Education, Philadelphia, PA 19104, USA.
authors.forename: Dustin M
authors.initials: DM
authors.lastname: Bermudez
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Canning
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002921:Cicatrix / Q000503:physiopathology*; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D016133:Polymerase Chain Reaction; D013521:Urologic Surgical Procedures, Male / Q000379:methods*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8