EFFECT OF ORAL PREDNISONE ON AIRWAY INFLAMMATORY MEDIATORS IN ATOPIC ASTHMA

The mechanism of steroid action in asthma is unknown. Because steroids have effects in vitro on eicosanoid synthesis, we determined the effe ct of oral prednisone for 6 to 9 days on eicosanoid levels in bronchoa lveolar lavage (BAL) fluid of 14 atopic asthmatic volunteers at baseli ne and after allergen instillation. We also determined the effect of p rednisone on the ex vivo release of eicosanoids from macrophage-rich B AL-fluid cells. Prednisone reduced symptoms and inhaler use but had no significant effect on BAL-fluid eicosanoid levels. At baseline, prost aglandin D-2 (PGD(2)) levels were 101 a 37 pg/ml in BAL fluid (mean +/ - SEM), versus 66 +/- 18 pg/ml after prednisone; likewise, 5-hydroxy e icosatetraenoic acid (5-HETE) levels were 59 +/- 15 versus 78 +/- 21; leukotriene E(4) (LTE(4)) 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 PGD(2) were 1274 +/- 565 vers us 1468 +/- 679 after prednisone; likewise, allergen-stimulated 5-HETE levels were 95 +/- 21 versus 82 +/- 21; those of LTE(4) were 54 +/- 2 0 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. LTB(4) levels fell significantly from 35 +/ - 6.4 ng/10(6) BAL-fluid cells to 17 +/- 5.4 after prednisone; likewis e, levels of thromboxane B-2 (TXB(2)) fell from 35.7 +/- 7.5 to 20.7 /- 6.6. Part of the action of steroids may involve alteration in macro phage eicosanoid synthesis.