A comparison of the inhibitory effects of budesonide, beclomethasone dipropionate, dexamethasone, hydrocortisone and tixocortol pivalate on cytokine release from leukocytes recovered from human bronchoalveolar lavage.
OBJECTIVE
The potency of budesonide, beclomethasone dipropionate (BDP), dexamethasone, hydrocortisone and tixocortol pivalate as inhibitors of interleukin-5 (IL-5) and interferon-gamma (IFNgamma) release from human bronchoalveolar lavage cells in vitro were compared.


METHODS
BAL leukocytes were obtained from patients undergoing bronchoscopy for diagnostic purposes. BAL leukocytes were activated with PHA (10 microg/ml) and PMA (10 ng/ml) and cultured for 48 h in the presence or absence of glucocorticoids. Culture supernatants were assayed for cytokines by ELISA.


RESULTS
Budesonide (10(-9) to 10(-7) M) and BDP (10(-8) to 10(-6) M) were the most potent glucocorticoids tested. Dexamethasone (10(-7) to 10(-5) M) was less potent, and the maximum inhibitory effect of dexamethasone was less than that produced by than budesonide or BDP. Tixocortol pivalate (10(-6) to 3 x 10(-5) M) caused a concentration-related inhibition of IL-5 release but only the highest concentration tested inhibited the release of IFNgamma. Hydrocortisone (10(-4) M) inhibited IL-5 and IFNgamma release.


CONCLUSIONS
We conclude that, unlike the other glucocorticoids tested, tixocortol pivalate appeared to be a selective inhibitor of IL-5 release. Possible mechanisms for this selectivity are discussed.
Whelan
C J
CJ
Department of Biosciences, University of Hertfordshire, Hatfield, Herts, UK.
Payne
A N
AN
Planquois
J M
JM
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001507:Beclomethasone / Q000494:pharmacology; D018893:Bronchoalveolar Lavage; D019819:Budesonide / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D010835:Phytohemagglutinins; D019819:Budesonide; C019112:tixocortol pivalate; D003907:Dexamethasone; D001507:Beclomethasone; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone