Interleukin-4-independent production of Th2 cytokines by nasal lymphocytes and nasal eosinophilia in murine allergic rhinitis.
BACKGROUND
Interleukin (IL)-4 is believed to play an important role in the atopic pathogenesis. However, the precise role of IL-4 in the in vivo initiation of allergic rhinitis is not fully understood. We have recently found that BALB/c mice sensitized intranasally with Schistosoma mansoni egg antigen (SEA) mount a Th2 response that initiates allergic rhinitis. Thus, we sought to determine the role of IL-4 in the initiation of allergic rhinitis in vivo with this model.


METHODS
IL-4 gene-deficient (IL-4 -/-) BALB/c and wild-type (IL-4 +/+) control mice were sensitized by intranasal SEA administration, and their immunologic responses were examined both in vivo and in vitro.


RESULTS
IL-4 +/+ mice sensitized with SEA displayed significantly higher titers of SEA-specific IgG1 and IgE antibodies than IL-4-/- mice, while the latter produced significantly more SEA-specific IgG2a. Antigen-stimulated nasal lymphocytes from SEA-sensitized IL-4 -/- and IL-4 +/+ mice produced similar amounts of IL-5 and IL-10, but neither produced IFN-gamma. Furthermore, the severity of nasal eosinophilia was similar in both groups.


CONCLUSIONS
These results indicate that although IL-4 is necessary for the production of Th2-associated antibodies--in particular, IgE--it is not required for either the production of the Th2-associated cytokines IL-5 and IL-10, or the induction of nasal eosinophilia.
Okano
M
M
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Satoskar
A R
AR
Abe
M
M
Harn
D A
DA
Okano
M
M
Nishizaki
K
K
Takeda
Y
Y
Yoshino
T
T
Brombacher
F
F
Satoskar
A A
AA
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000947:Antigens, Helminth / Q000494:pharmacology; D002478:Cells, Cultured; D004802:Eosinophilia / Q000503:physiopathology*; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012550:Schistosoma mansoni / Q000276:immunology; D018418:Th2 Cells / Q000378:metabolism*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007074:Immunoglobulin G; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma