IL-13 is essential to the late-phase response in allergic rhinitis.
BACKGROUND
The pathophysiology of the early- and late-phase nasal response to allergen challenge is not completely defined. Recent technical advances enable direct monitoring of these responses in mice.


OBJECTIVE
IL-13 is detected in the nasal membranes of both human beings and mice with allergic rhinitis, but its role in disease pathogenesis is unclear. We measured early and late nasal allergic responses after treatment with soluble IL-13Ralpha2-IgG fusion protein (sIL-13Ralpha2-Fc), and in IL-13-deficient mice (IL-13(-/-)).


METHODS
IL-13(-/-) mice (BALB/c background) and wild-type mice were sensitized to ovalbumin by intraperitoneal injection and then challenged intranasally with ovalbumin without sedation. The sIL-13Ralpha2-Fc or control human IgG was administered by intraperitoneal (i.p.) injection 24 hours and 1 hour before each ovalbumin challenge. Early nasal responses after the 4th ovalbumin challenge and late nasal responses 24 hours after the 6th ovalbumin challenge were assessed.


RESULTS
Sensitized/challenged wild-type mice treated with sIL-13Ralpha2-Fc or IL-13(-/-) mice demonstrated significantly reduced late nasal responses in face of persistent nasal tissue eosinophilia; the early nasal response was little affected by targeting IL-13. Goblet cell hyperplasia was not detected in nasal membranes.


CONCLUSIONS
The data indicate that IL-13 is a major contributor to the development of a late nasal response with little influence on the early response, and without affecting nasal eosinophilic inflammation. Inhibition of IL-13 may have an important therapeutic application in preventing the persistent nasal blockage in allergic rhinitis.


CONCLUSIONS
Current therapies for allergic rhinitis may not take into account the important differences in the pathophysiology of the early and late responses and the important role of IL-13 in sustaining chronic nasal congestion and obstruction.
Miyahara
Satoko
S
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Miyahara
Nobuaki
N
Matsubara
Shigeki
S
Takeda
Katsuyuki
K
Koya
Toshiyuki
T
Gelfand
Erwin W
EW
D000818:Animals; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D018793:Interleukin-13 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D013997:Time Factors
D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D010047:Ovalbumin