Blockade of IL-33/ST2 ameliorates airway inflammation in a murine model of allergic asthma.
OBJECTIVE
Interleukin (IL)-33 is involved in the development of lung inflammation by inducing or amplifying Th2 type-mediated responses in various animal models of allergic asthma. The ST2 gene is a member of the IL-1 receptor family, producing a transmembrane form (ST2L) and a soluble secreted form (sST2). sST2 has been shown to block this IL-33/ST2 signaling pathway. This study aimed to investigate whether anti-IL-33 and sST2 reduced airway inflammation in a murine model of asthma.


METHODS
BALB/c mice were sensitized and challenged with ovalbumin (OVA), and the effect of sST2 and anti-IL-33 antibody on airway inflammation and airway hyperresponsiveness (AHR) was evaluated. Furthermore, we measured changes in various cytokines in the bronchoalveolar lavage (BAL) fluid when treated with sST2 or anti-IL-33.


RESULTS
We observed that anti-IL-33 antibody and sST2 exert a negative regulation on OVA-mediated allergic airway inflammation. Both treatments reduced total cell counts and eosinophil counts in BAL fluid and AHR to methacholine. The Th2 cytokines, such as IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after both treatments. However, there were no changes in the level of TGF- ß1 and IL-10 after each treatment.


CONCLUSIONS
These results suggest that anti-IL-33 as well as sST2 have therapeutic potential for allergic asthma through inhibition of Th2 cytokine production.
1Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Hea Yon
HY
Lee
Chin Kook
CK
Rhee
Ji Young
JY
Kang
Ji Hae
JH
Byun
Joon Young
JY
Choi
Seung Joon
SJ
Kim
Young Kyoon
YK
Kim
Soon Suk
SS
Kwon
Sook Young
SY
Lee
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000139:chemically induced* / Q000150:complications* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects*; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D007074:Immunoglobulin G; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D007073:Immunoglobulin E; D010047:Ovalbumin