Dexamethasone and cyclosporin A suppress mast cell-leukocyte cytokine cascades by multiple mechanisms.
Based on in vitro findings with mouse mast cells and in vivo findings in mice, we report that dexamethasone or cyclosporin A can have at least three actions which interfere with the pathogenesis IgE-, mast-cell-, and cytokine-dependent inflammatory reactions: suppression of the IgE-dependent increase in tumor necrosis factor (TNF)-alpha mRNA by mast cells, inhibition of the IgE-dependent production of TNF-alpha protein by mast cells, and diminution of the responsiveness of target cells to TNF-alpha. Our findings in mice raise the possibility that similar actions of these agents in humans may account for some of the clinical efficacy of corticosteroids and cyclosporin A in allergic diseases.
Wershil
B K
BK
Combined Program in Pediatric Gastroenterology, Children's Hospital, Boston, Mass., USA.
Furuta
G T
GT
Lavigne
J A
JA
Choudhury
A R
AR
Wang
Z S
ZS
Galli
S J
SJ
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D007073:Immunoglobulin E / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D003907:Dexamethasone; D016572:Cyclosporine