THE HERBAL MEDICINE UNKEI-TO STIMULATES CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT PRODUCTION IN THE PITUITARY FOLLICULO-STELLATE-LIKE CELL-LINE (TTT GF)/

PROBLEM: We previously reported that a cytokine-induced neutrophil che moattractant (CINC) was produced in the pituitary gland and that it in fluenced anterior pituitary hormone release. In this study we investig ated the effect of Unkei-to, a Japanese herbal medicine, on CINC produ ction in the rat anterior pituitary gland and the pituitary folliculo- stellate-like cell line (TtT/GF). METHOD OF STUDY: Dispersed normal an terior pituitary cells and the folliculo-stellate-like cell line TtT/G F were used to test the effect of Unkei-to on CINC secretion and CINC mRNA accumulation. Concentrations of CINC in the conditioned media wer e measured by an enzyme-linked immunosorbent assay, and levels of CINC mRNA were analyzed by Northern blot analysis. RESULTS: Unkei-to (20 m u g/ml) significantly increased the secretion of CINC by normal anteri or pituitary cells within 12 hr of incubation. Unkei-to also stimulate d CINC secretion from TtT/GF cells in a time-and dose-dependent manner . Unkei-to (20 mu g/ml) increased CINC mRNA accumulation in TtT/GF cel ls within 3 hr of incubation and also caused a 13-fold increase in the secretion of CINC from TtT/GF cells compared with the vehicle group w ithin 24 hr of incubation. Finally, we found that some of the Unkei-to 's ingredients, Evodiae fructus and Pinelliae tube,, markedly stimulat ed CINC secretion from TtT/GF cells. CONCLUSIONS: Our results will hel p to elucidate the mechanism behind the clinical effect of Unkei-to on the anterior pituitary gland. They also suggested the presence of spe cial substances, which stimulate CINC secretion, within Unkei-to's ing redients such as E. fructus and P. tuber.