IL-12 regulates bone marrow eosinophilia and airway eotaxin levels induced by airway allergen exposure.
BACKGROUND
Airway allergen exposure causes local eosinophilic cell infiltration. This cellular inflammatory response is likely to involve the release of eosinophils from peripheral storage pools, and possibly also regeneration of eosinophils in the bone marrow. IL-12 is an inhibitory cytokine in allergic inflammation, shown to reduce eosinophilic cell infiltration. The aim of the present study was to determine whether airway allergen exposure increases bone marrow eosinophil production, and, if so, whether IL-12 modulates this effect.


METHODS
Ovalbumin-sensitized C57BL/6 mice and IL-12 knockout (KO) mice were exposed to allergen via the airway route, and the inflammatory cell response was evaluated in bronchoalveolar lavage fluid, blood, and bone marrow.


RESULTS
Allergen instillation intranasally produced a dose-dependent inflammatory response in the lower airways of sensitized mice. This inflammatory response was dominated by eosinophils, but there were also increases of both lymphocytes and neutrophils. Sensitization and airway allergen exposure also increased the IL-5-dependent growth of bone marrow cells in vitro. The enhanced bone marrow responsiveness in vitro was paralleled by an increased number of bone marrow eosinophils in vivo. After sensitization and repeated allergen exposure, IL-12 KO mice showed higher eosinophil levels in both BAL and bone marrow than parallel wild-type control mice. Furthermore, BAL-eotaxin levels were increased in IL-12 KO mice as opposed to parallel wild-type controls after allergen exposure.


CONCLUSIONS
Airway allergen exposure induced systemic immunologic responses, including increased eosinophil numbers in both airways and bone marrow, and also enhanced IL-5 responsiveness in bone marrow cells. IL-12 may regulate airway eosinophilia at both the level of eosinophilopoiesis and the level of local recruitment of eosinophils into the airways.
Zhao
L L
LL
Department of Respiratory Medicine and Allergology, Göteborg University, Gothenburg, Sweden.
Lindén
A
A
Sjöstrand
M
M
Cui
Z H
ZH
Lötvall
J
J
Jordana
M
M
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018929:Cell Culture Techniques; D054413:Chemokine CCL11; D019742:Chemokines, CC; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D018664:Interleukin-12 / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D011657:Pulmonary Eosinophilia / Q000097:blood / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D018664:Interleukin-12; D010047:Ovalbumin