Induction of cytokine expression in the brain macrophages/amoeboid microglia of the fetal rat exposed to a teratogen.

Using in situ hybridization, RT-PCR, lectin histochemistry and immunohistochemistry, this study examined the time course expression and cellular localization of various cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-1, IL-6) and transforming growth factor-beta (TGF-beta) in fetal rat brain after a maternal injection of the teratogen cyclophosphamide (CP). Eight hours after CP injection, there was a marked increase in brain macrophages (BM)/amoeboid microglia (AM) in different areas of the fetal brain as determined by lectin histochemistry. Concomitant to this was the induction in mRNA level of TNF-alpha, which was progressively increased with time. TGF-beta mRNA was undetectable until 24 h had elapsed. Expression of IL-1 and IL-6 was undetectable at all stages. In situ hybridization combined with immunohistochemistry has shown the localization of TNF-alpha in BM/AM and neurons. Present results suggest that both TNF-alpha and TGF-beta are involved in the progression of neural damage in the fetal brain induced by the teratogen.