The effect of different corticosteroids and cyclosporin A on interleukin-4 and interleukin-5 release from murine TH2-type T cells.
By secretion of interleukin-4 and interleukin-5, TH2-type T cells are thought to play an important role in the pathogenesis of asthma. Corticosteroids are currently the most effective therapy available for asthma, but recently it has been demonstrated that cyclosporin A improves lung function in patients with severe corticosteroid-dependent asthma. In order to examine the effects of corticosteroids and cyclosporin A on anti-CD3-induced production of interleukin-4 and interleukin-5 we used the murine TH2-type cell clone D10.G4.1. Interleukin-4/interleukin-5 release was inhibited by all drugs tested with the following IC50 values (nmol/l) for interleukin-4 and interleukin-5, respectively: budesonide (0.32/0.22), beclomethasone (0.65/0.33), dexamethasone (4.70/3.52), 6 alpha-methyl-prednisolone (24.04/17.02), hydrocortisone (34.27/22.55), and cyclosporin A (72.59/242.21). In conclusion, corticosteroids exert strong inhibitory effects on cytokine production by TH2-cells, which may explain, at least partly, its clinical efficacy in asthma. Cyclosporin A also showed a concentration-dependent inhibition; however, in relation to corticosteroids the inhibitory activity of cyclosporin A was found to be weaker.
Schmidt
J
J
Department of Pharmacology, ASTA Medica AG, Frankfurt/Main, Germany.
Fleissner
S
S
Heimann-Weitschat
I
I
Lindstaedt
R
R
Szelenyi
I
I
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D015847:Interleukin-4 / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015848:Interleukin-5; D015847:Interleukin-4; D016572:Cyclosporine