IL‐1 is required for allergen‐specific Th2 cell activation and the development of airway hypersensitivity response

S Nakae, Y Komiyama, H Yokoyama… - International …, 2003 - academic.oup.com
S Nakae, Y Komiyama, H Yokoyama, A Nambu, M Umeda, M Iwase, I Homma, K Sudo…
International immunology, 2003academic.oup.com
IL‐1 is a pro‐inflammatory cytokine consisted of two molecular species, IL‐1α and IL‐1β,
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 Th2 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‐1α/β‐deficient (IL‐1α/β–/–) mice was
significantly reduced from the levels seen in wild‐type mice, whereas the responses seen in …
Abstract
IL‐1 is a pro‐inflammatory cytokine consisted of two molecular species, IL‐1α and IL‐1β, 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 Th2 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‐1α/β‐deficient (IL‐1α/β–/–) 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 Th2 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‐1α/β–/– mice were markedly reduced compared with these responses in wild‐type mice; such responses were enhanced in IL‐1Ra–/– mice. Using IL‐1α–/– and IL‐1β–/– mice, we determined that both IL‐1α and IL‐1β are involved in this reaction. Both IgG1 and IgE levels were reduced in IL‐1β–/– mice, while only IgE levels were affected in IL‐1α–/– mice, indicating a functional difference between IL‐1α and IL‐1β. These observations indicate that IL‐1 plays important roles in the development of AHR.
Oxford University Press