Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist decarboethoxy-loratadine and dexamethasone by human mast and basophilic cell lines.
Mast cells and basophils are central effector cells of allergic reactions and are involved in inflammatory diseases. These cell types produce an array of mediators including a broad spectrum of cytokines. In order to examine whether antiallergic drugs modulate the release of these mediators, we have investigated the influence of dexamethasone and decarboethoxy-loratadine (DEL), the active metabolite of the H1-blocking agent loratadine, on the release of IL-6 and IL-8 by the human mast cell line HMC-1 and the human basophilic cell line KU812 by ELISA. Dexamethasone (10(-6)-10(-11) M) or Del (10(-5)-10(-14) M) were added to the cells either 1 h prior to or simultaneously with PMA and Ca-ionophore A23187. When preincubated with the cells, DEL dose-dependently suppressed IL-6 release by up to 40% and IL-8 release by up to 50%. Dexamethasone potently suppressed secretion of both cytokines if simultaneously added to the cells with the stimuli by up to 60% and after preincubation by up to 80%. Since both antihistamines and glucocorticoids are used for treatment of allergic diseases, the findings reported here indicate that these drugs may modulate allergic reactions via inhibition of cytokine release from mast cells and basophils.
Department of Dermatology, Virchow Klinikum, Humboldt Universität, Berlin, Germany.
U
U
Lippert
S
S
Krüger-Krasagakes
A
A
Möller
U
U
Kiessling
B M
BM
Czarnetzki
D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D017336:Loratadine / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism
D006634:Histamine H1 Antagonists; D015850:Interleukin-6; D016209:Interleukin-8; D017336:Loratadine; D003907:Dexamethasone