Eosinophil activation status and corticosteroid responsiveness in severe asthma.
BACKGROUND
Since eosinophils are implicated in asthma pathogenesis, we investigated whether these cells were activated in severe asthma.


METHODS
Twenty-six asthmatics with different clinical responses to oral corticosteroid (CS), i.e. sensitive [change in forced expiratory volume in 1 s (DeltaFEV(1)) >/= 25% after oral methylprednisolone, 40 mg daily, for 14 days, n = 7], resistant (DeltaFEV(1) </= 15%, n = 9) and dependent (>/= 20 mg oral prednisone daily for acceptable asthma control, n = 10), were studied.


RESULTS
Calcium ionophore-induced leukotriene (LT) C(4) release of purified blood eosinophils was similar in the three groups. Cell incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced ionophore-induced LTC(4) release, and this effect was higher in CS-sensitive (5-fold) than in CS-resistant subjects (1.7-fold) (p = 0.02). CS treatment decreased blood eosinophil counts in these two groups of subjects (p </= 0.02) and decreased GM-CSF-enhanced LTC(4) release in CS-sensitive asthmatics only (p = 0.04). In contrast, despite a high mean daily dose of oral CS (35 +/- 8 mg), blood counts of eosinophils from CS-dependent subjects were higher (p = 0.03) and GM-CSF enhancement of LTC(4) release was greater (2.8-fold) than in CS-sensitive (2. 1-fold) and CS-resistant (1.7-fold) subjects (p = 0.04). Interestingly, serum from CS-resistant subjects reduced GM-CSF enhancement of LTC(4) release by eosinophils of CS-sensitive asthmatics (p = 0.001).


CONCLUSIONS
Eosinophils from CS-dependent asthmatics have an impaired response to CS, whereas serum from CS-resistant subjects contains an inhibitor of eosinophil response to GM-CSF.
Bossé
M
M
Unité de Recherche, Centre de Pneumologie de l'Hôpital Laval, Centre Hospitalier Universitaire de Québec, Université Laval, Ste-Foy, Québec, Canada.
Audette
M
M
Laflamme
G
G
Ferland
C
C
Boulet
L P
LP
Laviolette
M
M
D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D002478:Cells, Cultured; D004351:Drug Resistance; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D013224:Status Asthmaticus / Q000188:drug therapy*
D000305:Adrenal Cortex Hormones; D017997:Leukotriene C4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor