IL-13 may mediate allergen-induced hyperresponsiveness independently of IL-5 or eotaxin by effects on airway smooth muscle.
IL-13 is a mediator of allergen-induced airway hyperresponsiveness (AHR). The aim of this study was to evaluate whether eotaxin and IL-5 were implicated in the effects of IL-13 on allergen-induced AHR or whether IL-13 may exert its effects through direct actions on airway smooth muscle (ASM). To study this question airway inflammation and AHR were induced in mice by sensitization and subsequent challenge on three successive days with ovalbumin. A monoclonal anti-IL-13 antibody administered before each challenge significantly reduced AHR without affecting airway eosinophilia. No changes of mRNA in BAL and lung tissues or protein levels in BAL of IL-5 or eotaxin were found following anti-IL-13 treatment. Combined injection of monoclonal anti-IL-5 and antieotaxin antibodies before each antigen challenge blocked airway eosinophilia but failed to reduce AHR. IL-13 induced calcium transients in cultured murine ASM cells and augmented the calcium and contractile responses of these cells to leukotriene D4. These results suggest that IL-13 plays an important role in allergen-induced AHR and is important in the early phases of the inflammatory process. Its effects on AHR are mediated independently of IL-5 and eotaxin and may involve a direct effect on ASM to augment its responsiveness.
Eum
Seok-Yong
SY
Deparment of Microbiology, Yonsei University College of Medicine, Seoul, South Korea.
Maghni
Karim
K
Tolloczko
Barbara
B
Eidelman
David H
DH
Martin
James G
JG
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology; D001991:Bronchitis / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007114:Immunization; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D015848:Interleukin-5 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000503:physiopathology*
D000485:Allergens; D000906:Antibodies; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D018793:Interleukin-13; D015848:Interleukin-5; D012333:RNA, Messenger; D002118:Calcium