Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone: role of eosinophils, IL-5, eotaxin, and IL-13.
BACKGROUND
Glucocorticoids inhibit allergen-induced airway eosinophilia and airway hyperresponsiveness (AHR). Whether glucocorticoids mediate their effects on AHR by inhibiting eotaxin and IL-5, 2 of the principal mediators of eosinophilia, or through IL-13, an important mediator of AHR, has not been established.


OBJECTIVE
We sought to investigate the effects of glucocorticoids on airway eosinophilia and the expression of IL-5, eotaxin, and IL-13 in relation to the induction of AHR in a murine model of allergic asthma.


METHODS
Dexamethasone (4 mg/kg) and mAbs against eotaxin (80 micro g/kg) and IL-5 (100 micro g/kg) singly and in combination were administered to immunized mice before antigen challenge. Airway responsiveness to methacholine was measured in anesthetized and mechanically ventilated animals. Eotaxin, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), lung homogenates, or both were measured by means of ELISA.


RESULTS
A single antigen challenge induced AHR that lasted at least 10 days. Eotaxin protein and mRNA levels increased in lung tissue but not in BALF after challenge. IL-5 protein and mRNA levels increased both in BALF and in lung tissue. Dexamethasone reduced airway eosinophilia, AHR, and protein and mRNA for eotaxin and IL-5. Anti-murine eotaxin and anti-IL-5 antibodies alone and in combination reduced the ovalbumin-induced airway eosinophilia significantly but failed to inhibit AHR. Both dexa-methasone and anti-IL-5/anti-eotaxin inhibited the increases in lung IL-13 levels after ovalbumin challenge to a similar extent.


CONCLUSIONS
These findings suggest that the inhibition of AHR by the glucocorticoid dexamethasone does not appear to be explained by effects on eosinophilia, eotaxin, IL-5, or IL-13.
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Canada.
Seok-Yong
SY
Eum
Karim
K
Maghni
Qutayba
Q
Hamid
David H
DH
Eidelman
Holly
H
Campbell
Susumu
S
Isogai
James G
JG
Martin
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000235:genetics / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D004804:Eosinophils / Q000502:physiology*; D018793:Interleukin-13 / Q000502:physiology*; D015848:Interleukin-5 / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D011657:Pulmonary Eosinophilia / Q000517:prevention & control*; D012333:RNA, Messenger / Q000032:analysis
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D018793:Interleukin-13; D015848:Interleukin-5; D012333:RNA, Messenger; D003907:Dexamethasone