Ra. Pauwels et al., CYTOKINE MANIPULATION IN ANIMAL-MODELS OF ASTHMA, American journal of respiratory and critical care medicine, 156(4), 1997, pp. 78-81
Citations number
32
Categorie Soggetti
Emergency Medicine & Critical Care","Respiratory System
We have developed in C57 Black 6 mice an in vivo model of allergic air
way inflammation characterized by the presence of IgE antibodies to an
inhaled antigen, peribronchial infiltrates with an increased number o
f eosinophils, and an increased airway responsiveness to nonantigenic
bronchoconstrictor stimuli. In this animal model we have investigated
the role of different cytokines in the development of IgE antibodies t
o inhaled antigen, eosinophilic airway inflammation, and airway hyperr
esponsiveness. The studies were performed by using knockout mice or by
exogenous administration of cytokines or cytokine antagonists. Interl
eukin-4 (IL-4) knockout mice were unable to develop an allergic eosino
philic airway infiltration and did not produce specific IgE antibodies
. Chronic aerosol exposure to antigen also did not induce an increase
in airway responsiveness. In studies of wildtype mice, pretreatment wi
th the combination of anti-IL5 and anti-IL5 receptor antibodies, given
in an attempt to fully inhibit the effect of endogenously released IL
-5, caused a pronounced inhibition of the antigen-induced airway eosin
ophilia but did not prevent the increase in airway responsiveness. Tre
atment with IL-12 during the active immunization prevented airway eosi
nophilia, production of specific IgE antibodies, and the antigen-induc
ed increase in airway responsiveness. In contrast, administration of I
L-12 to actively immunized mice during the aerosol exposure abolished
airway eosinophilia and airway hyperresponsiveness without affecting t
he production of specific IgE.