Two-Track Medical Treatment Strategy According to the Clinical Scoring System for Chronic Rhinosinusitis

Kim, Dong-Kyu,Kang, Seong Il,Kong, Il Gyu,Cho, Young Hoon,Song, Seul Ki,Hyun, Se Jin,Cho, Sung Dong,Han, Sang-Yoon,Cho, Seong-Ho,Kim, Dae Woo The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

<P><B>Purpose</B></P><P>The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application.</P><P><B>Methods</B></P><P>A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators.</P><P><B>Results</B></P><P>The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses.</P><P><B>Conclusions</B></P><P>The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.</P>

다탐색(多探索) 법을 통한 저자극성 액체 세정제 조성물 개발

김배환 ( Peter Kim ),현기안 ( Ki-an Hyeon ),정지윤 ( Ji-youn Chung ),윤삼숙 ( Sanm-sook Yoon ),강한철 ( Han Chyul Kang ),박선희 ( Sun Hee Park ),고강일 ( Kang Il Ko ),김기호 ( Ki Ho Kim ) 대한화장품학회 2005 대한화장품학회지 Vol.31 No.1

세정제에 널리 상용화되어 있는 알킬에톡시설페이트 계의 음이온 계면활성제는 피부 흡착의 특성 때문에 충분히 헹구어 내지 않으면 피부에 잔존되어 자극의 원인이 되어 염증 반응을 일으키게 된다. 따라서 기존의 음이온 계면활성제를 대체 또는 보완하기 위해 기존의 계면활성제들을 단백질 변성 실험, 세포 독성 그리고 IL-1α 측정을 통해 선별하였다. 본 연구는 저자극성의 음이온 또는 비이온, 양쪽성 이온의 14종의 계면활성제와 민감성 피부를 위해 제조된 13종의 기존 세정제 제품에 대한 세포독성을 실시하여, 가장 독성이 낮은 계면활성제로 sodium laureth sulfate (음이온), sodium cocoyl isethionate (음이온), sodium lauroamphoacetate (양성이온), cocamidopropyl betaine (양성이온), alkyl polyglycoside (비이온)가 선택되었고 2종의 기존 세정제 제품을 비교 제형으로 선택하였다. 5종의 계면활성제를 20종의 formulation으로 제조하여 단백질 변성(<3M SLS (13.2%)), 세포독성 실험 및 폐첩포 실험을 통하여 다시 5종을 선별하였다. 이들 제형을 진피 배양으로 세포독성 및 IL-1α 방춘량을 조사하여 가장 자극이 낮은 계면활성제 제형을 선택하였으며, 첨가된 계면활성제의 자극을 완화하기 위하여 항염과 보습 효과가 우수한 마치현 추출물(3%, 5%)과 fructan (3%, 5%)을 농도별로 첨가한 제형을 제조하여 가장 안전성이 뛰어난 농도를 선택하였다. 최종적으로 선택된 제형 5번을 3차원 세포 배양을 통한 인공피부를 이용하여 가장 자극이 낮게 나타난 기존의 제품들과 세포 독성 및 IL-1α 방출량을 비교 조사하여 저자극성의 액체 세정제를 개발하였다. Alkyl ethoxy sulfate type surfactants, widely used in commercial cleansers, are easily adsorbed to skin to often cause skin irritation and inflammation if not thoroughly rinsed nut. In order to replace or complement existing surfactants, we screened the existing surfactants through protein denaturation method, cell cytotoxicity assay and human IL-1α assay, etc. Fourteen surfactants have been chosen from among too irritant anionic, cationic and/or zwitter-ionic ones and investigated for cell cytotoxicity in human fibroblast cell lines using monolayer culture with the thirteen commercially available cleansers for sensitive skin. From these results, we selected 5 surfactants and 2 commercial cleansers (names not shown), such as sodium laureth sulfate (anionic), sodium cocoyl isethionate (anionic), sodium lauroamphoacetate (zwitter-ionic), and cocamidopropyl betaine (zwitter-ionic), alkyl polyglycoside (non-ionic). 20 formulations were made out of 5 surfactants and five of them were chosen through a protein denaturation method (lower than 3 M sodium dodecyl sulfate solution (13.2%)), cell cytotoxicity and human patch test. These five selected formulations containing preservatives were compared to two selected commercial cleansers by cell cytotoxicity and human IL-1α ELISA assay using dermal equivalent. Finally, we selected the best formulation. To this formulation, fructan (3% or 5%) or/and portulaca extract (3% or 5%) well known for its anti-inflammatory and moisturizing effects were added and investigated for cell cytotoxicity using dermal equivalent. In cytotoxicity assay using dermal equivalent, two formulations containing 5% fructan and 3% or 5% portulaca extract were less toxic than the others. In cytotoxicity assay and human IL-1α ELISA using 3D culture, the selected formulation containing 5% fructan and 5% portulaca extract showed better efficiency than those of the others and 2 commercial cleansers. As a result, we could develop a low irritant and safe liquid cleanser.

주조직적합항원이 불일치하는 마우스 동종 조혈모세포이식에서 IL-2로 유도된 CD4+CD25+ T세포를 이용한 이식편대숙주병의 억제

현재호,정대철,정낙균,박수정,민우성,김태규,최병옥,김원일,한치화,김학기,Hyun, Jae Ho,Jeong, Dae Chul,Chung, Nak Gyun,Park, Soo Jeong,Min, Woo Sung,Kim, Tai Gyu,Choi, Byung Ock,Kim, Won Il,Han, Chi Wha,Kim, Hack Ki 대한면역학회 2003 Immune Network Vol.3 No.4

Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

Tobacco Smoking Could Accentuate Epithelial-Mesenchymal Transition and Th2-Type Response in Patients With Chronic Rhinosinusitis With Nasal Polyps

Lee Ki-Il,Han Younghwan,Ryu Jae-Sung,In Seung Min,Kim Jong-Yeup,Park Joong Su,Kim Jong-Seok,Kim Juhye,Youn Jubin,박석래 대한면역학회 2022 Immune Network Vol.22 No.4

Tobacco smoking (TS) has been known as one of the most potent risk factors for airway inflammatory diseases. However, there has been a paucity of information regarding the immunologic alteration mediated by TS in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). To identify the effect of TS, we harvested human tissue samples (never smoker: n=41, current smoker: n=22, quitter: n=23) and analyzed the expression of epithelial-derived cytokines (EDCs) such as IL-25, IL-33, and thymic stromal lymphopoietin. The expressions of Th2 cytokines and total serum IgE showed a type-2 inflammatory alteration by TS. In addition, the epithelial marker E-cadherin and epithelial-mesenchymal transition (EMT)-associated markers (N-cadherin, α-SMA, and vimentin) were evaluated. Histological analysis showed that EDC expressions were upregulated in the current smoker group and downregulated in the quitter group. These expression patterns were consistent with mRNA and protein expression levels. We also found that the local Th2 cytokine expression and IgE class switching, as well as serum IgE levels, were elevated in the current smoker group and showed normal levels in the quitter group. Furthermore, the expressions of E-cadherin decreased while those of N-cadherin, α-SMA, and vimentin increased in the current smoker group compared those in the never smoker group. Taken together, these results indicate that TS contributes to the deterioration of pathogenesis by releasing local EDCs and Th2 cytokines, resulting in EMT in patients with CRSwNP. We verified that alterations of immunological response by TS in sinonasal epithelium can play a vital role in leading to CRSwNP.

Effects of Moxibustion to Zusanli(ST36) on Alteration of Natural Killer Cell Activity in Rats

Choi, Gi Soon,Han, Jae Bok,Park, Joon Ha,Oh, Sang Deog,Lee, Gi Seog,Bae, Hyun Su,Jung, Sung Ki,Cho, Young Wuk,Ahn, Hyun Jong,Min, Byung Il WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2004 東西醫學硏究所 論文集 Vol.2004 No.-

Moxibustion is one of the major healing techniques in Oriental medicine. It has been widely used in many diseases such as rheumatoid arthritis, Hashimoto disease, breech presentation, etc. However, till now, effects of moxibustion on natural killer (NK) cell activity and relations between sympathetic nerve system (SNS) and the immune alteration induced by moxibustion wert not well studied. This study was designed to evaluate effects of moxibustion on NK cell activity and the Intervention of SNS in the alteration of NK cell activity induced by moxibustion. Splenic NK cell cytotoxicity was measured in a standard 4-hour ^(51)Cr release assay. We measured the NK cell cytotoxicity after moxibustion stimulation for 1, 3, 5 and 7 days, and also measured the NK cell cytotoxicity after 3 and 7 days burn stimulation with similar temperature. Interleukin (IL)-2, -4 and interferon (INF)-γ in serum were measured by rat IL-2, -4 and INF-γ ELISA test kit. To evaluate the effects of sympathectomy on alteration of NK cell cytotoxicity, 6-hydroxydopamine (6-OHDA: 50 mg/kg) was used. We showed that NK cell activity of moxibustion stimulation group incrcased at the 3rd day, and declined at the 7th day in comparison with that of the control group. In thc moxibustion stimulation group, NK cell activity was significantly higher than the sham group at the 3rd day. On the contrary, in the burn stimulation group, NK cell activity was significantly higher than that of the sham groups at 3rd and 7th days. INF-γ level after 3 days in the moxibustion stimulation group was significantly higher than that of the sham group. IL-2 Ievel among groups were not different. IL-4 was not detected in serum with this method. Sympathectomy abolished the NK cell activity alteration induced by moxibustion. The results suggest that moxibustion modulates NK cell activity, along with INF-γ, and SNS is mediating these effects.

골수이식 후 사이토카인과 골교체 생화학적표지자의 변화 및 상관관계

민우성,강무일,한제호,강성구,오기원,이원영,김혜수,문성대,손현식,신완식,김춘추,윤건호,차봉연,이광우,손호영 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.1

Background : Loss of bone mass is usually detected after BMT. The causes of bone loss are related with gonadal dysfunction and immunosuppressants. Cytokines, especially IL-6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study is to assess the relationship of bone turnover markers and cytokines of peripheral blood and bone marrow before and after allogeneic BMT. Methods : This prospective study included two analyses. The first was a study of 46 BMT recipients, examining the relationship between bone turnover markers and cytokines of serum which were measured before and 1, 2, 3, 4 week and 3 months after BMT. The second was a study of 14 BMT patients, measuring bone marrow plasma cytokines such as IL-6 and TNF-? at post-BMT 3 week and bone turnover marker at the same time to assess the relationship beween two parameters. Results : Serum ICTP, bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. There was positive correlation between serum ICTP and bone marrow IL-6 levels at the post-BMT 3 week with a statistical significance, but the correlation between bone turnover markers and bone marrow TNF-? or peripheral blood cytokines was not found. Conclusion : Our data suggest that the progressive increase of bone resorption after BMT is related with the increase of bone marrow IL-6, which is a potent stimulator of bone resorption in vivo(J Kor Soc Endocrinol 15:85-96, 2000).

제왕절개술 환자에서 수술전 투여한 ketamine의 혈청 interleukin-6 및 수술후 통증에 대한 효과

김진수,김유재,안기량,김천숙,김일호,한찬수 순천향의학연구소 1997 Journal of Soonchunhyang Medical Science Vol.3 No.2

The inflammatory reaction to tissue damage during surgery may induce central sensitization followed by hyperalgesia. Previous studies suggest that central sensitization is related to N-methyl-D-aspartate (NMDA) receptor activation, which can be blocked with NMDA antagonist, ketamine. Thus, we compared the effect of preoperative intravenous and epidural low doses of ketamine with placebo on serum interleukin-6 (IL-6) level and postoperative pain. ASA class I and II women scheduled for C-sections received intravenous ketamine 0.15mg/kg(group 2) or placebo(group 1), or epidural ketamine(0.15 mg/kg) before the operation. IL-6 levels were measured before and during the operation, and 8, 24, and 48 hrs after the operation. Visual Analogue Scales(VAS) and Verbal Ration Scales(VRS) were measured at 8, 24, and 48 hrs after the operation. Serum IL-6 levels at 8, 24, and 48 hrs after the operation were significantly lower in the intravenous ketamine and epidural ketamine groups than in the control group. VAS at 8 hrs and 48 hrs after the operation were significantly lower in the epidural ketamine group. VAS at 8 hrs and 48 hrs after the operation were significantly lower in the epidural ketamine group than in the control and intravenous ketamine groups. In conclusion, in the preoperative intravenous and epidural administration of low doses(0.15mg/kg) of ketamine, both are effective in reducing postoperative IL-6 levels. Epidural Ketamine is more effective than intravenous ketamine in postoperative pain control.

상승된 경악반응으로 측정한 조건화된 공포에 대한 다이아제팜, 로라제팜, 요힘빈의 영향

한정수,김재일,김기석 한국심리학회 1997 한국심리학회지 생물 및 생리 Vol.3 No.1

본 연구의 목적은 조직화된 공포를 측정하는 상승된 경악반응 모델을 이용해 벤조나이아제핀 수용기에 작용하는 약물인 다이아제팜, 로라제팜과 알파2-아드레날린 수용기에 작용하여 중추신경계에서 노에피네플린을 증가시키는 요힘빈이 공포의 발현에 어떠한 역할을 하는지, 그리고 다이아제팜, 로라제팜을 투여전, 요힘빈 투여가 상승된 경악반응에 어떠한 영향을 주는지를 알아보고자 한다. 조건자극(빛)과 무조건자극(전기충격: 1.0㎃)을 이틀간 20번 짝지워 제시한 후, 그 다음날 경악반응 측정전에 여섯집단에 식염수(0.1cc/㎏), 다이아제팜(1.25㎎/㎏), 로라제팜(1.25㎎/㎏), 요힘빈(0.25㎎/㎏), 다이아제팜과 요힘빈, 로라제팜과 요힘빈을 투여했다. 식염수를 투여받은 동물들은 빛과 경악자극(강한 소리자극) 제시시 경악자극만을 제시한 경우보다 높은 경악반응을 보였지만, 상승된 경악반응은 요힘빈을 투여한 동물보다 낮았다. 다이아제팜, 로라제팜과 이 약물들을 요힘빈과 함께 투여한 집단들은 상승된 경악반응을 보이지 않았다. 이 결과로 보아, 요힘빈은 중추신경계에 작용하는 노에피네플린을 증가시켜 공포의 발현을 촉진시키는 반면 다이아제팜과 로라제팜은 공포의 발현을 억제하고 이들 약물의 사전처치는 요힘빈의 촉진효과을 적지함을 알 수 있다. This study was conducted to examine whether diazepam and lorazepam acting on benzodiazepine receptors have any effect on the expression of fear in potentiated startle, whether or not yohimbine which acts in α2-adrenergic receptors and increases norepinphine in central nervous system have any role, and how pretreatment of diazepam or lorazepam influences the yohimbine's effect. Ten conitioning trials, in which light was paired with shock(1.0㎃), were presented on each of two successive training days, and on the following day each of six groups were injected respectively saline(0.1cc/㎏), diazepam(1.25㎎/㎏), lorazepam(1.25㎎/㎏), yohimbine(0.25㎎/㎏), yohimbine after diazepam, and yohimbine after lorazepam before measuring the startle responses. Results showed that the saline-injected animals exhibit higher startle response than only in the presence of startle stimulus(intense auditory stimulus) when they were presented light and startle stimulus, but the response magnitude was less than that of yohimbine-injected animals. For diazepam group, lorazepam group, and yohimbine-added group, the animals did not show potentiated startle response. Taken together, yohimbine increases norepinephine in central nervous system and elicits fear easily while diazepam and lorazepam inhibit fear.

아급성 연합성 변성의 선경전도 검사

권기한,선우일남,정근호 대한신경과학회 1999 대한신경과학회지 Vol.17 No.2

내측회장동맥에 의해 형성된 척수경막동정맥루로 인한 척수병증 1예

이일형,배재천,이상무,김진혁,권기한,이병철 대한신경과학회 1999 대한신경과학회지 Vol.17 No.3