Human first trimester forebrain cells express genes for inflammatory and anti-inflammatory cytokines

Using in situ hybridization and immunohistochemistry the induction of poten tial cytokines [interleukin 1 beta (IL-1 beta), IL-4, IL-6, IL-10, tumour n ecrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transfor ming growth factor beta (TGF-beta)] in human embryonic forebrain cells at w eeks 5, 7 and 10 of gestation was studied. The aims were to investigate the capacity of these cells to express cytokines, to determine the kinetics of induction and to display the type of cytokine expressing cells in the deve loping brain. Constitutive cytokine gene expression was recorded from week 5, augmented by about 50% at week 7 and by more than 100% at week 10 (excep t TGF-beta at week 10), Among other cytokines, IL-1 beta exhibited the high est expression at week 10, TGF-beta showed maximum expression at week 7 and declined at week 10, Combined techniques revealed that glial cells are a m ajor source of cytokines, The study show and present for the first time the kinetics of spontaneous cytokine expression in human embryonic forebrain c ells. The increased mRNA expressions with age suggest an important role for cytokines in promotion of brain development. The capacity of inducing thes e cytokines may, however, be implicated in the immunopathogenesis of severa l brain diseases. The distinctive TGF-beta profile suggests a further role for TGF-beta on modulation of cytokine responses during development. (C) 19 99 Academic Press.