The effects of IL-5 on airway physiology and inflammation in rats.
BACKGROUND
There is evidence that the cytokine IL-5 is a prominent feature of airway inflammation in asthma.


OBJECTIVE
The aim of this study was to determine whether exogenous IL-5 could cause changes in lung physiology, the early and late airway response after antigen challenge, and airway inflammation in rats that do not have a propensity to develop these changes after sensitization and challenge.


RESULTS
Intratracheal administration of IL-5 to ovalbumin sensitized Brown Norway SSN rats increased the airway responsiveness to methacholine (AHR) 20 hours after administration of IL-5 at the same time as an increase in neutrophils occurred in the lung lavage. This effect was dose dependent and was not caused by endotoxin. Concurrent intratracheal administration of 50 ng of anti-IL-5 monoclonal antibody with 10 microg of recombinant human IL-5 decreased the AHR and neutrophil influx. Pretreatment with 3 microg of IL-5 had no effect on the early and late airway response or on AHR after ovalbumin challenge. However, IL-5 increased lung re-sistance 20 hours after antigen challenge. Although total lung cells and differential counts did not differ significantly 8 hours after antigen challenge, the blood lymphocyte CD4/CD8 ratio decreased in IL-5 pretreated rats (P <.05). In addition, in situ hybridization showed a significant increase in cells within the airway wall expressing IL-4 and IL-5 mRNA in IL-5 treated/challenged rats compared to controls (P <.05).


CONCLUSIONS
The intratracheal administration of IL-5 causes only part of the physiologic changes that are associated with asthma. Other factors are necessary to obtain the complete asthma phenotype.
Nag
Sammy S
SS
CHUM Research Center, Notre Dame Pavillion, University of Montreal, and the Meakins-Christie Laboratories, McGill University, Quebec, Canada.
Xu
Li Jing
LJ
Hamid
Qutayba
Q
Renzi
Paolo M
PM
D000818:Animals; D001773:Blood Cells / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000473:pathology; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000503:physiopathology; D015848:Interleukin-5 / Q000008:administration & dosage / Q000494:pharmacology*; D007442:Intubation, Intratracheal; D008168:Lung / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012137:Respiratory System / Q000187:drug effects* / Q000503:physiopathology*; D012140:Respiratory Tract Diseases / Q000503:physiopathology*; D013234:Stem Cells / Q000473:pathology
D016207:Cytokines; D015848:Interleukin-5; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin