R Dworski, GA Fitzgerald, JA Oates and JR Sheller
Department of Medicine and Experimental Therapeutics, University College, Dublin, Ireland.

The mechanism of steroid action in asthma is unknown. Because steroids have effects in vitro on eicosanoid synthesis, we determined the effect of oral prednisone for 6 to 9 days on eicosanoid levels in bronchoalveolar lavage (BAL) fluid of 14 atopic asthmatic volunteers at baseline and after allergen instillation. We also determined the effect of prednisone on the ex vivo release of eicosanoids from macrophage- rich BAL-fluid cells. Prednisone reduced symptoms and inhaler use but had no significant effect on BAL-fluid eicosanoid levels. At baseline, prostaglandin D2 (PGD2) levels were 101 +/- 37 pg/ml in BAL fluid (mean +/- SEM), versus 66 +/- 18 pg/ml after prednisone; likewise, 5-hydroxy eicosatetraenoic acid (5-HETE) levels were 59 +/- 15 versus 78 +/- 21; leukotriene E4 (LTE4) levels were 35 +/- 13 versus 51 +/- 21, and 15- hydroxy eicosatetraenoic acid (15-HETE) levels were 29 +/- 8 versus 19 +/- 7. Allergen-stimulated levels of PGD2 were 1274 +/- 565 versus 1468 +/- 679 after prednisone; likewise, allergen-stimulated 5-HETE levels were 95 +/- 21 versus 82 +/- 21; those of LTE4 were 54 +/- 20 versus 91 +/- 51; and those of 15-HETE were 63 +/- 19 versus 60 +/- 25. Prednisone reduced the synthesis of eicosanoids in macrophage-rich BAL- fluid cells in vitro. LTB4 levels fell significantly from 35 +/- 6.4 ng/10(6) BAL-fluid cells to 17 +/- 5.4 after prednisone; likewise, levels of thromboxane B2 (TXB2) fell from 35.7 +/- 7.5 to 20.7 +/- 6.6. Part of the action of steroids may involve alteration in macrophage eicosanoid synthesis.

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