Ji Won Lee
,
Seoul National University Medical Research Center, Seoul, South Korea
Da-Eun Park
,
Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, South Korea
Boram Bae
,
Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, seoul, South Korea
Hyun Seung Lee
,
Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, South Korea
Mingyu Kang, MD
,
Internal Medicine, Subdivision of Allergy, Chungbuk National University Hospital, Cheongju, South Korea
Han-Ki Park, MD
,
Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, South Korea
Soon-Hee Kim
,
Seoul National University Bundang Hospital, Seoul, South Korea
Woo-Jung Song, MD
,
Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
Hye-Ryun Kang, MD, PhD
,
Regional Pharmacovigilance Center, Seoul National University Hospital, Seoul, South Korea
Heung Woo Park, MD, PhD
,
Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
Yoon-Seok Chang, MD, PhD
,
Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
Chang-Han Park
,
Department of Internal Medicine, Sung-Ae General Hospital, Seoul, South Korea
Suk-Il Chang
,
Department of Internal Medicine, Sung-Ae General Hospital, Seoul, South Korea
Sook-Hee Song, MD, PhD
,
Internal Medicine, Seoul Medical Center, Seoul, South Korea
Kyung-up Min, MD, PhD
,
Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, South Korea
Sang-Heon Cho, MD, PhD
,
Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, South Korea
Background: Recent epidemiological studies demonstrate significant associations of Staphylococcal enterotoxins (SE) with asthma. In addition, clinical studies suggest that the enterotoxin exposure could contribute to the development of fixed airway obstruction in asthma, leading to a COPD-overlap phenotype. In previous experiments of mice, a short-term exposure to staphylococcal enterotoxin B (SEB) induced extensive inflammatory responses in lungs, including lymphocytes, neutrophils and eosinophils. Therefore, we hypothesized chronic repeated exposure to SEB could induce tissue remodeling in lower airways.
Objective: To investigate effects of repeated SEB exposure on airway remodeling in OVA-induced chronic allergic asthma model.
Methods: BALB/c mice were intra-peritoneally sensitized with ovalbumin (OVA)-aluminum hydroxide at days 0 and 14, and were intra-nasally challenged with OVA and/or SEB for the next 6 weeks(50 ug OVA, 10 or 100 ng of SEB, 3 times per week over a period, total 18 exposure). At 8 weeks, mice were sacrificed and assessed for histopathology, bronchoalveolar lavage fluid (BALF) cell counts, lung cytokines, methacholine airway hyper-responsiveness (AHR), and serum immunoglobulins.
Results: OVA sensitization followed by repeated OVA exposure resulted in the development of Th2 asthma and inflammation, including BALF cell counts, lung cytokines, histopathology, AHR and serum immunoglobulins. However, repeated SEB exposure did not aggravate OVA-induced pathologic changes, or induce any remarkable pathologic changes when administered alone. Serum total IgE levels were also not influenced by repeated SEB exposure. Rather, chronic repeated SEB-exposed mice showed lower levels of lung inflammation and remodeling, but higher levels of IL-10 and TGF-β, compared to non-SEB-exposed mice.
Conclusion: The present study demonstrates unpredicted suppressive effects of chronic repeated exposure of SEB in allergic asthma models, leading to the speculation that SEB exerts bi-directional effects depending on the timing of exposure. The mechanisms of anti-inflammatory effects warrant further investigation.
