BAL eotaxin and IL-5 in asthma, and the effects of inhaled corticosteroid and beta2 agonist.
OBJECTIVE
In a longitudinal ex vivo placebo-controlled study, asthmatics already treated with inhaled corticosteroid received supplemental long-acting beta-agonist (LABA) or increased doses of their inhaled corticosteroid (ICS). Previously reports have shown significant reductions in biopsy eosinophil numbers after treatment with LABA. Following these findings, eosinophil chemokines eotaxin and IL-5 in the BAL fluid at baseline and after 3 months of study medication have now been measured, and these data with that from new cross-sectional controls have also been compared. It is hypothesised that changes in airway eosinophils would be related to eosinophil cytokines.


METHODS
BAL cytokines were measured by chemiluminescent enzyme-linked immunosorbent assay, while eosinophils were measured by immunohistochemistry or differential cell counting. For all measures, longitudinal data were compared to that from ICS-free asthmatics (n = 42) and non-asthmatic controls (n = 28).


RESULTS
BAL eotaxin in asthmatics was elevated above non-asthmatic levels regardless of ICS levels. BAL IL-5 was elevated in ICS-free asthmatics, but not in asthmatics on low-dose ICS treatment. Longitudinally, BAL eotaxin was unchanged after 3 months. Unexpectedly, IL-5 increased after 3 months of additional LABA treatment but was not further affected by increasing the dose of ICS. Airway eotaxin seemed to be constitutively raised in asthmatics, whereas, IL-5 levels were more steroid-responsive. No relationship was observed between eosinophils and eosinophilic cytokines in the BAL.


CONCLUSIONS
While the elevation of luminal IL-5 with LABA treatment cannot be accounted for, it may have contributed to luminal clearance of airway wall eosinophils. The lack of correlation between airways eosinophils and eosinophilic cytokines in the BAL is particularly important.
Feltis
Bryce N
BN
Respiratory Research Group, Tasmanian School of Medicine, University of Tasmania, Hobart, Tasmania, Australia. bryce_feltis@hotmail.com
Reid
David W
DW
Ward
Chris
C
Walters
E Haydn
EH
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis*; D003430:Cross-Sectional Studies; D000068298:Fluticasone; D006801:Humans; D015848:Interleukin-5 / Q000032:analysis*; D008137:Longitudinal Studies; D000068299:Salmeterol Xinafoate; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D001993:Bronchodilator Agents; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015848:Interleukin-5; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol