Am. J. Respir. Crit. Care Med., Vol 151, No. 1, 01 1995, 177-183.
Antibody to interleukin-5 inhibits virus-induced airway hyperresponsiveness to histamine in guinea pigs
AJ van Oosterhout, I van Ark, G Folkerts, HJ van der Linde, HF Savelkoul, AK Verheyen and FP Nijkamp
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
In humans, respiratory viral infections lead to increased airway
responsiveness and exacerbations of asthma. In the present study, the role
of interleukin-5 (IL-5) in virus-induced airway hyperresponsiveness and
inflammation was examined in guinea pigs. In animals treated with control
antibody, parainfluenza-3 virus significantly potentiated (219%) the
histamine-induced increase in lung resistance compared with vehicle
treatment. In addition, viral infection significantly increased (130 to
450%) the responsiveness of isolated tracheal segments to histamine in
animals treated with control antibody. In guinea pigs treated with control
antibody, the numbers of eosinophils (226%), neutrophils (1,380%), and
monocytes (626%) in bronchoalveolar lavage fluid were significantly
increased after viral infection. The level of major basic protein in
bronchoalveolar lavage fluid was not altered after viral infection. In
addition, electron microscopic examination of eosinophils in airway tissue
and alveolar lumen did not point to increased degranulation after viral
infection. In guinea pigs treated with antibody to IL-5 the virus-induced
airway hyperresponsiveness to histamine both in vivo and in vitro was
almost completely inhibited. In guinea pigs treated with anti-IL-5, viral
infection significantly increased the numbers of eosinophils (234%),
neutrophils (1,255%), and monocytes (617%) in bronchoalveolar lavage fluid.
These data suggest that IL-5 plays an important role in airway
hyperresponsiveness to histamine but not in the infiltration of eosinophils
after respiratory viral infection.
