Endotoxin-stimulated release of cytokines by cultured cells from the murine neurohypophysis: role of dexamethasone and indomethacin.
It is well established that many cell types produce inflammatory cytokines and we were interested to see whether cells in the neurohypophysis had this ability. This study examines the effect of lipopolysaccharide (LPS) on cytokine production in cultured murine neural lobe (NL) cells. Cells were cultured from the neurohypophysis of mice not older than 5 days and the experiments were performed after 12 days in culture. The majority of cells in culture were immunoreactive for glial fibrillary acidic protein, indicating that the cells were pituicytes. Cytokines were measured in 24-hour samples using commercial ELISA kits. Cells growing in a medium free of endotoxin released 94.3 +/- 6.6 pg IL-6/NL/24 h (mean +/- SEM, n = 21). The release of interleukin-6 (IL-6) was reversible and increased concentration dependently with LPS in the concentration range of 0.1-1 ng/ml. The addition of 1 ng/ml LPS increased the IL-6 release 12-fold to a maximum value of 1,134 +/- 85.5 pg IL-6/NL/24 h (mean +/- SEM, n = 6). No trace of interleukin-1beta (IL-1beta) (<3 pg/NL/24 h) or tumor necrosis factor-alpha (<10 pg/NL/24 h) was detected after LPS stimulation. We examined the effect of dexamethasone (10(-6) M) and indomethacin (10(-4) M) on the release of IL-6 in submaximally stimulated cells. Dexamethasone inhibited the unstimulated and the LPS-stimulated release of IL-6 by 70 and 81%, respectively. Indomethacin had no influence on the release, and it is concluded that cyclooxygenase is not involved in the response. A close association exists between the membrane of the neurosecretory endings and the pituicytes in the neurohypophysis. This naturally raises the question as to whether IL-6 might reflect a physiological connection between the two cell types.
Hansen
E W
EW
Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen, Denmark. ewh@maildfh.dk
Malling
D
D
Christensen
J D
JD
D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D003907:Dexamethasone; D007213:Indomethacin