CCR3 Monoclonal Antibody Inhibits Eosinophilic Inflammation and Mucosal Injury in a Mouse Model of Eosinophilic Gastroenteritis

송대진,심문희,이나현,유영,정지태 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.4

Purpose: Although the role of eosinophils in eosinophilic gastroenteritis (EGE) is not fully understood, they are believed to be a principal effector cell. Previous studies have demonstrated that eotaxin and its specific receptor, cysteine-cysteine chemokine receptor-3 (CCR3), play a central role in eosinophil trafficking into the gastrointestinal (GI) tract. Thus, we examined the targeting of CCR3 as a potential therapeutic intervention for EGE in a mouse model. Methods: Eight- to 10-week-old BALB/c mice were intraperitoneally sensitized and intragastrically challenged with ovalbumin (OVA). Different groups of mice were administered either an anti-CCR3 antibody or a control IgG by intraperitoneal injection 1 hour before each OVA challenge. Eosinophilic inflammation in the intestinal mucosa, mucosal injury, and severity of diarrhea were compared between different groups at 1 hour after final OVA challenge. Results: Anti-CCR3 antibody reduced the number of eosinophils in peripheral blood and intestinal mucosa, but not in bone marrow. This reduction was associated with restoration of reduced villous crypt ratio, increased intestinal epithelial cell proliferation, and weight loss induced by OVA challenge. However, Anti-CCR3 antibody had no effect on the level of OVA specific immunoglobulin E (IgE) and the expression of critical chemokines or cytokines in eosinophil trafficking into the GI tract, such as eotaxin-1, interleukin (IL)-5, and IL-13. Conclusions: Anti-CCR3 antibody significantly reduced the severity of eosinophilic inflammation, mucosal injury, and diarrhea in a mouse model of food allergeninduced GI eosinophilic inflammation. CCR3 may be a novel therapeutic target for treatment of EGE and other GI eosinophil-mediated diseases.

VEGF and Activated Eosinophils in Children with Asthma and Eosinophilic Bronchitis

김경원,지혜미,이경은,박여훈,손명현,김규언,최봉석 대한 소아알레르기 호흡기학회 2009 Allergy Asthma & Respiratory Disease Vol.19 No.2

Purpose : Vascular endothelial growth factor (VEGF) is an important mediator of airway inflammation and remodeling in asthma. We aimed to explore whether VEGF is expressed at elevated levels in asthmatic airways or eosinophilic bronchitis (EB) and associated with eosinophilic inflammation, pulmonary function, and airway hyperresponsiveness (AHR) in children. Methods : One hundred seventeen asthmatic children, 77 children with EB, and 84 healthy children were enrolled. Sputum supernatants were collected and VEGF and eosinophil cationic protein (ECP) levels were measured. Results : Asthmatic children had significantly higher levels of VEGF in induced sputum [89.04 (29.95-178.09) pg/mL] compared to children with EB [25.30 (11.02-80.23) pg/mL] and healthy children [37.37 (16.56-71.30) pg/mL; P=0.0003]. VEGF in sputum positively correlated with sputum ECP (r=0.524; P<0.0001). Negative significant correlations were found between sputum VEGF and FEV1, (r=-0.252; P=0.001) or post-bronchodilator FEV1 (r=-0.181; P= 0.038) whereas nonsignificant correlations were found between sputum VEGF and sputum eosinophils. Conclusion : Our findings suggest that VEGF is associated with activated eosinophils in the asthmatic airway, but not EB. Sputum VEGF could be a supportive marker that represents activation of airway eosinophils and persistent airflow limitation in asthmatic children. Purpose : Vascular endothelial growth factor (VEGF) is an important mediator of airway inflammation and remodeling in asthma. We aimed to explore whether VEGF is expressed at elevated levels in asthmatic airways or eosinophilic bronchitis (EB) and associated with eosinophilic inflammation, pulmonary function, and airway hyperresponsiveness (AHR) in children. Methods : One hundred seventeen asthmatic children, 77 children with EB, and 84 healthy children were enrolled. Sputum supernatants were collected and VEGF and eosinophil cationic protein (ECP) levels were measured. Results : Asthmatic children had significantly higher levels of VEGF in induced sputum [89.04 (29.95-178.09) pg/mL] compared to children with EB [25.30 (11.02-80.23) pg/mL] and healthy children [37.37 (16.56-71.30) pg/mL; P=0.0003]. VEGF in sputum positively correlated with sputum ECP (r=0.524; P<0.0001). Negative significant correlations were found between sputum VEGF and FEV1, (r=-0.252; P=0.001) or post-bronchodilator FEV1 (r=-0.181; P= 0.038) whereas nonsignificant correlations were found between sputum VEGF and sputum eosinophils. Conclusion : Our findings suggest that VEGF is associated with activated eosinophils in the asthmatic airway, but not EB. Sputum VEGF could be a supportive marker that represents activation of airway eosinophils and persistent airflow limitation in asthmatic children.

Respiratory syncytial virus 세기관지염에서비세척액내 호산구성 염증에 대한 TNF-α 역할

최준기,허경,김효빈,윤운기,김창근 대한 소아알레르기 호흡기학회 2008 Allergy Asthma & Respiratory Disease Vol.18 No.1

Purpose:Tumor necrosis factor-α (TNF-α) and eosinophilic inflammation have their role in asthma, but there were no studies on respiratory syncytial virus (RSV) bronchiolitis. The aim of our study was to investigate whether TNF-α has a role in eosinophilic inflammation of lower respiratory tract infections with RSV and has the correlation with other cytokines. Methods:Fifty children with first RSV bronchiolitis (RSV group) and 18 healthy children without any respiratory symptom and sign (control group) were enrolled. Clinical data, such as eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), were analyzed. We measured interleukin (IL)-5, IL-8, TNF-α, granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-γ, eotaxin, and regulated on activation, normal T cell expressed and secreted (RANTES) in nasal lavage fluid in both groups. Results:Eotaxin, GM-CSF, IL-8, IFN-γ and TNF-α were higher in the RSV group than the control group. TNF-α correlated with an eosinophil-active cytokine, GM-CSF (r=0.86, P< 0.0001), IFN-γ (r=0.90, P<0.0001), and with eosinophil-active C-C chemokines such as eotaxin (r=0.50, P<0.0001). TNF-α also correlated with proinflammatory cytokines such as IL-8 (r= 0.81, P<0.0001). Conclusion:TNF-α correlated with eosinophil-active chemokines and cytokines. Therefore, TNF-α may have a role in eosinophilic inflammation in children with RSV bronchiolitis. Purpose:Tumor necrosis factor-α (TNF-α) and eosinophilic inflammation have their role in asthma, but there were no studies on respiratory syncytial virus (RSV) bronchiolitis. The aim of our study was to investigate whether TNF-α has a role in eosinophilic inflammation of lower respiratory tract infections with RSV and has the correlation with other cytokines. Methods:Fifty children with first RSV bronchiolitis (RSV group) and 18 healthy children without any respiratory symptom and sign (control group) were enrolled. Clinical data, such as eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), were analyzed. We measured interleukin (IL)-5, IL-8, TNF-α, granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-γ, eotaxin, and regulated on activation, normal T cell expressed and secreted (RANTES) in nasal lavage fluid in both groups. Results:Eotaxin, GM-CSF, IL-8, IFN-γ and TNF-α were higher in the RSV group than the control group. TNF-α correlated with an eosinophil-active cytokine, GM-CSF (r=0.86, P< 0.0001), IFN-γ (r=0.90, P<0.0001), and with eosinophil-active C-C chemokines such as eotaxin (r=0.50, P<0.0001). TNF-α also correlated with proinflammatory cytokines such as IL-8 (r= 0.81, P<0.0001). Conclusion:TNF-α correlated with eosinophil-active chemokines and cytokines. Therefore, TNF-α may have a role in eosinophilic inflammation in children with RSV bronchiolitis.

위배출시간의 지연을 동반한 호산구성 위염 1예

배선윤,정호중,김미연,이미래,이혁 대한소화기내시경학회 2009 Clinical Endoscopy Vol.39 No.5

Eosinophilic gastritis is a rare disease that is characterized by eosinophilic infiltration of the bowl wall tissue, and the presentation of symptoms varies depending on the affected site. It is likely that eosinophil-active cytokines play important roles in this disease. A 22-year old man presented with abdominal pain and vomiting. Endoscopic gastric biopsy revealed eosinophilic infiltration, and the serum level of Interleukin (IL)-5 was increased. Gastric emptying was moderately delayed in this patient. The patient was treated with steroid and he showed dramatic clinical improvement with disappearance of the eosinophilic infiltration of the gastric mucosa, normalization of the serum level of IL-5 and improvement of the gastric emptying time. There has been few case reports of eosinophilic gastritis that have described the change of the serum level of cytokines and the gastric emptying. We report here on a case of eosinophilic gastritis and the patient showed elevated serum level of cytokines and delayed gastric emptying. The patient improved after being treated with steroid. 호산구성 위염은 장벽의 병적인 호산구 침윤을 특징으로 한 드문 질환으로, 장관내의 침범 부위에 따라 다양한 임상 증상을 나타낼 수 있으며, 호산구의 활성화와 관련된 사이토카인이 질환에서 중요한 역할을 한다고 알려져 있다. 복통과 구토를 주소로 내원한 환자의 내시경을 통한 위 조직 검사 상에서 호산구의 침윤이 관찰되었고, 혈청 IL-5가 상승되어 있음을 확인하였다. 또한 위 운동장애 여부를 확인하기 위해 시행한 위배출시간 검사에서 중등도의 지연 소견을 보였다. 스테로이드 투여 후 증상의 호전과 함께 조직의 호산구 침윤의 소실, 혈청 IL-5의 정상화 및 위배출시간의 정상화를 확인할 수 있었다. 국내에서 호산구성 위염의 치료 경과에 따른 혈청 사이토카인 및 위배출시간의 변화를 관찰한 예는 아직 보고가 없으며, 저자들은 사이토카인의 상승 및 위배출시간의 지연을 동반한 호산구성 위염에서 스테로이드 투여 후 호전된 예를 경험하여 문헌고찰과 함께 보고한다.

복수를 동반한 호산구성 위장염 1례

한승묵,신원승,김민수,김정희,김성종,정재진,이동욱,이동욱,곽동협 啓明大學校 醫科大學 1998 계명의대학술지 Vol.17 No.3

호산구성 위자염은 툭발성으로 위장관 벽의 호산구 침윤과 말초 혈액내 호산구증다증을 동반하고 다양한 위장관 증상을 나타내는 질환으로 복수가 동반된 경우는 매우 드문 것으로 알려져 있다. 이에 저자들은 최근에 말초 혈액에 호산구증다증과 장점막의 호산구 침윤뿐만 아니라 소산구성 복수가 동반되고 스테로이드 요법으로 잘 치료된 호산구성 위장염 1례를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Eosinophilic gastroenteritis is an uncommon disease of uncertain etiology characterized by eosinophilia in the peripheral blood and eosinophilic infiltrates in the bowel wall. Clinical features vary depending on which layers or regions of the gastrointestinal tract are mainly affected. Mucosal involvement causes malabsorption. protein-losing enteropathy and diarrhea. Infiltration of the muscle layer manifests gastric outlet or small bowel obstruction. Serosal involvement causes an exudative ascites rich in eosinophils. Eosinophilic gastroenteritis with ascites is a rare from of eosinophilic gastroenteritis. In this paper, we present a case of eosinophilic gastroenteritis with ascites demonstrating eosinophilia in the peripheral blood and eosinophilic infiltrates in the mucosal wall. The patient was successfully treated with steroid therapy. In addition to this case report, the several literatures on eosinophilic gastroentritis are reviewed.

Assessment of factors associated with disease severity and prognosis for acute eosinophilic pneumonia patients

최준영,임정욱,이진국 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.0

Objective: The object of this study was to investigate factors associated with disease severity and prognosis in acute eosinophilic pneumonia (AEP) patients. Methods: We retrospectively reviewed medical records of AEP patients treated at Armed Forces Capital Hospital between May 2012 to May 2017. To assess disease severity of the disease, we analyzed correlations of PF ratio with BAL/blood eosinophil, smoking days and CRP. To investigate prognostic factors, we defined poor prognosis group as patients with prolonged O2 demand (≥2 days). We performed logistic regression on prognosis with age, BAL eosinophil/blood eosinophil, smoking days and CRP. Results: Among total of 344 patients, 99.7% of patients were male and mean age was 20.4±1.4. Only 0.6% of patients were never smoker and mean smoking days were 26.2±25.4. PF ratio showed significant correlation with BAL eosinophil (r=0.207, p<0.01), blood eosinophil (r=0.140, p=0.05), smoking days (r=-0.154, p=0.04) and CRP (r=-0.184 p=0.01). Simple logistic regression on prognosis revealed that CRP (OR=1.07; 95% CI, 1.02-1.11), blood eosinophil (OR=0.87; 95% CI, 0.80-0.93), smoking days (OR 1.01; 95% CI, 1.00-1.02) were statistically significant. By multiple logistic regression, blood eosinophil (OR=0.88; 95% CI, 0.80-0.95) and smoking days (OR 1.01; 95% CI, 1.00-1.02) were significant factors associated with disease prognosis. Conclusions: In this study, severity of AEP was correlated with BAL/blood eosinophil, smoking days and CRP. Furthermore, disease prognosis was revealed to be associated with blood eosinophil and smoking days.

호산구성 세포염 (Wells' 증후군) -1예 보고-

이안희 대한병리학회 1995 Journal of Pathology and Translational Medicine Vol.29 No.3

A Rare Case of Eosinophilic Gastroenteritis in a Neonate with Fever

Minkyeong Lee,최소윤,정미림,이종현,성명순 대한신생아학회 2019 Neonatal medicine Vol.26 No.4

Eosinophilic gastroenteritis is a member of eosinophilic gastrointestinal (GI) diseases and is characterized by the accumulation of eosinophils within the GI tract. Common symptoms of eosinophilic gastroenteritis are vomiting, abdominal pain, dysphagia, and weight loss, but rare fever in neonate. This report describes a 10-day-old boy who developed fever, bloody mucoid stool, and bilious vomiting resulting from eosinophilic gastroenteritis, mimicking sepsis. Sigmoidoscopy and pathologic findings revealed mucosal edema, small hemorrhagic spot, and segmental erythemoid edema in the colon and increased number of eosinophils in the lamina propria with intraepithelial eosinophils. After breast milk feeding with restriction of milk from the mother for 6 months, specific immunoglobulin to milk was class 0 (class 3, previous). The boy restarted formula feeding, and he had no fever and GI symptoms.

Eosinophilic fasciitis in a patient with polymyositis

( Tae-rim Kim ),( Kihyuk Shin ),( Woo-il Kim ),( Won-ku Lee ),( Gun-wook Kim ),( Hoon-soo Kim ),( Hyun-chang Ko ),( Byung-soo Kim ),( Moon-bum Kim ),( Min-young Yang ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.1

Eosinophilic fasciitis (EF) is a rare connective tissue disease characterized by erythema and painful edema on extremities, followed by induration of the skin, with laboratory findings of peripheral eosinophilia, hypergammaglobulinemia. Histopathological findings in EF include increased thickness of the fascia with infiltration of lymphocytes, plasma cells, mast cells, eosinophils. The differential diagnosis includes scleroderma, morphea and any panniculitis. A 34-year-old man presented with stiffness of upper extremities for five months. The patient also complained of lesional pain and decreased mobility of the wrist and elbow joint that had occurred a month later. Left forearm MRI showed diffuse fascial T2 hyperintensity with enhancement along the deep and intermuscular fascia. Histopathologic findings revealed thickened fascia with infiltration of eosinophils, lymphocytes and plasma cells, and also showed myopathic change. The patient was diagnosed as EF with polymyositis, based on the clinical characteristics and histopathologic findings. Lesional pain and joint mobility was gradually improved after 10 months of systemic steroid and immunosuppressant. To our knowledge, EF is a rare disease and only 4 cases have been reported in Korean dermatology literature. Moreover, the case of EF with polymyositis has not been reported in Korea before. So we herein report a rare case of EF in a patient with polymyositis.

특집: 주요 알레르기질환의 진단과 치료 : 호산구성 폐렴의 진단과 치료

최동철 ( Dong Chull Choi ) 대한내과학회 2009 대한내과학회지 Vol.76 No.3

The eosinophilic lung diseases include various pulmonary disorders linked by common finding of an increased peripheral or tissue eosinophils. During the past decades, there has been a rapid increase in the understanding of eosinophil biology. However, there is no consensus about the classification and optimal treatment for eosinophilic lung diseases. Better understanding of the factors that regulate eosinophil traffic in the lung will leads us to better understanding of eosinophilic lung diseases. (Korean J Med 76:268-273, 2009)