IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response.
IL-1 is a pro-inflammatory cytokine consisted of two molecular species, IL-1alpha and IL-1beta, and the IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of both molecules. Although it is suggested that IL-1 potentiates immune responses mediated by T(h)2 cells, the role of IL-1 in asthma still remains unclear. In this study, we demonstrate that the ovalbumin (OVA)-induced airway hypersensitivity response (AHR) in IL-1alpha/beta-deficient (IL-1alpha/beta(-/-)) mice was significantly reduced from the levels seen in wild-type mice, whereas the responses seen in IL-1Ra(-/-) mice were profoundly exacerbated, suggesting that IL-1 is required for T(h)2 cell activation during AHR. OVA-specific T cell proliferation, IL-4 and IL-5 production by T cells, and IgG1 and IgE production by B cells in IL-1alpha/beta(-/-) mice were markedly reduced compared with these responses in wild-type mice; such responses were enhanced in IL-1Ra(-/-) mice. Using IL-1alpha(-/-) and IL-1beta(-/-) mice, we determined that both IL-1alpha and IL-1beta are involved in this reaction. Both IgG1 and IgE levels were reduced in IL-1beta(-/-) mice, while only IgE levels were affected in IL-1alpha(-/-) mice, indicating a functional difference between IL-1alpha and IL-1beta. These observations indicate that IL-1 plays important roles in the development of AHR.
Nakae
Susumu
S
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Komiyama
Yutaka
Y
Yokoyama
Hiroshi
H
Nambu
Aya
A
Umeda
Masaomi
M
Iwase
Michiko
M
Homma
Ikuo
I
Sudo
Katsuko
K
Horai
Reiko
R
Asano
Masahide
M
Iwakura
Yoichiro
Y
D000109:Acetylcholine / Q000494:pharmacology; D000485:Allergens / Q000276:immunology*; D000818:Animals; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000097:blood / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D012795:Sialoglycoproteins / Q000235:genetics / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; C507764:Il1rn protein, mouse; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin; D000109:Acetylcholine