Interleukin-1B(1L-1B) polymorphisms and gastric mucosal levels of IL-Iβ cytokine in Korean patients with gastric cancer

Chang, Young-Woon,Jang, Jae-Young,Kim, Nam-Hoon,Lee, Jae Won,Lee, Hyo Jung,Jung, Woon Won,Dong, Seok-Ho,Kim, Hyo-Jong,Kim, Byung-Ho,Lee, Joung-Il,Rin Chang KYUNG HEE UNIVERSITY MEDICAL CENTER 2006 고황의학상 수상논문집 Vol.21-22 No.-

Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1β and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1β cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR = 2.2; 95% CI = 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR = 3.4; 95% CI = 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1β levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1β production contributed to the development of intestinal-type GC in this Korean population.

화상환자에서 면역억제 기전

정태호,황일우,장수일,김문규,서정민,정치영,김정철 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.4

목적 : 본 연구는 화상환자에서 면역이상의 기전을 조사코져 T-세포의 활성을 나타내는 가용성 interleukin-2 수용체(IL-2R), 대식세포의 활성을 나타내는 neopterin, tumor necrosis factor(TNF) 및 interleukin-6 (IL-6), 그리고 호중구의 활성을 반영하는 elastase-α1-antitrypsin을 측정하였다. 또한 lipopolysaccharide(LPS)가 이들 면역세포의 활성화에 미치는 영향을 조사하였다. 대상 및 방법 : 30예의 화상환자를 대상으로 화상후 1일, 7일, 14일, 21일, 28일에 각각 혈액을 채취하여 혈청중 가용성 IL-2R, TNF, IL-6, 그리고 elastase-α1-antitrypsin은 각각 효소면역법으로, 혈청중 neopterin은 radioimmunoassay법으로 측정하였다. LPS가 말초 단핵세포에 미치는 영향은 역전사 중합효소 연쇄반응을 통하여 각종 cytokines의 mRNA 발현을 측정하였다. 결과 : 화상환자에서 혈청중 가용성 IL-2R은 화상후 1일째부터 대조군에 비하여 유의성 있게 증가되어 7일과 14일째에 최고치를 나타냈으며 그 이후에는 다소 감소하였으나 대조군보다는 유의한 증가를 나타냈다. 화상환자를 중화상, 중등도화상, 경도화상으로 분류하여 혈청중 가용성 IL-2R 치를 비교해본 결과 중증 화상일수록 더욱 높은 치를 나타냈다. 화상환자에서 혈청중 neopterin 역시 화상후 1일째부터 증가되어 전 관찰기간 동안 대조군에 비해 유의한 높은 치를 나타냈다. 경도화상과 중등도 화상에서는 서로 유의한 차이를 보이지 않았으나 중환자에서는 경도 혹은 중등도 화상환자에 비해 유의한 증가를 보였다. 화상환자에서 혈청중 TNF 농도는 화상후 1일부터 증가되어 관찰전기간에 걸쳐 유의한 증가를 나타냈으며 중등도 화상환자에서 가장 높은 치를 보였다. 혈청중 IL-6치 역시 화상 전기간에 걸쳐 대조군보다 유의한 증가를 나타냈으며 중화상 환자에서 가장 높은 치를 나타냈다. 화상은 또한 혈청중 elastase-α1-antitrypsin 농도를 현저히 증가시켰다. 즉 화상후 1일에 elastase-α1-antitrypsin 농도는 정상인보다 5배 높았으며 그 이후 약 4주간 계속 높은 농도를 유지하다가 환자가 회복되면서 감소하는 경향을 나타내었다. 중등도화상 및 중화상환자의 혈청중 elastase-α1-antitrypsin 농도는 경도 화상환자에서 비해 유의한 증가를 보였다. 한편 화상환자에서 면역이상을 초래하는 주된 요인으로 여겨지는 lipopolysaccharide는 면역세포를 총체적으로 활성화시켜 IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, IFN-γ, TGF-β, GM-CSF, IL-2R의 유전자발현을 현저히 증가시켰다. 결론 : 화상환자에서 T-세포, 대식세포, 호중구의 활성화를 반영하는 가용성 IL-2R, neopterin, ,TNF, IL-6, elastase-α1-antitrypsin치가 혈중에 증가되어 있으며 화상의 정도가 심할수록 더 높았다. Cell-mediated immunity frequently becomes severely impaired after thermal injury. However, the cause of postburn immune dysfunction is unclear and controversy exists over both pathophysiology and clinical relevance of these abnormalities. This study was undertaken to investigate the immune responses in vivo of patients with burn. Levels of soluble IL-2R, a sensitive marker of T-cell activation, levels of serum TNF, IL-6, and neopterin, an index of macrophage activation, and levels of serum elastase-α1-antitrypsin, an index of neutrophil activation, were measured in serial serum samples taken from 30 burned patients. In patients with burn, soluble IL-2R levels were increased over a 4-week interval with peak concentrations reached during the 2nd week after burn. Patients with severe burn showed a higher soluble IL-2R levels than those with mild or moderate burn. In addition soluble IL-2R significantly correlated with burn size. The levels of serum neopterin were already increased at the first day following burn, and remained at a high level throughout the total period studied (28 days). Patients with severe burn showed significantly higher concentration of serum neopterin than mild or moderate burn. There was positive relationship between the burn sizes and the levels of neopterin. A significant positive correlation was also found between serum soluble IL-2R levels and neopterin levels in burn patients. Levels of serum TNF and IL-6 were also significantly increased over a 4-week interval in burn patients. The levels of serum elastase-α1-antitrypsin were also already increased at the first day following burn, and remained at a high level over a 4-week. Patients with moderate or severe burn showed significantly higher concentration of serum elastase-α1-antitrypsin than those with mild burn. There was no significant relationship between the burn extent and the level of elastase-α1-antitrypsin. LPS increased the transcription of all the cytokines we examined in peripheral mononuclear cells, i.e., IL-1α, IL-1β, IL-2, IL-4, IL-5_IL-6, IL-8, IL-10, TNF, TGF-β, GM-CSF, and IL-2R. We conclude that soluble IL-2R, neopterin, TNF, IL-6, and elastase-α1-antitrypsin might be useful parameters for monitoring of the clinical course in burn patients. Moreover, they indicate that T-cell, macrophage, and neutrophil activation might play the central role in the pathogenesis of the immuno-logic and metabolic disturbance that follows thermal injury.

전치개교의 교정치료후 과두위치 변화

신수정,장영일 대한 두개하악장애학회 1993 대한두개하악장애학회지 Vol.5 No.2

ABSTRACTThis study was aimed to evaluate the changes in condylar position when severe anterior open bite pa- tients were treated with MEAW.The subjects consisted of 11 patients(21 TMJs) who visited the departement of orthodontics in SNUH, having severe anterior open bite as a chief complain. They were supposed to wear the up and down elas- tics and MEAW after finishing the leveling. The condylar position was evaluated with individualized cor- rected tomography in centric occlusion taken before and after treatment.The results were as follows; 1. In the change of condylar position after treatment, there were no statistically significant differences in right and left TMJs. 2. In the change of condylar position after treatment, there were no statistically significant differences in each malocclusion groups. 3. There were no statistically significant differences in percent dispacement of condyle between before and after treatment. 4. There were no statistically significant differences in the amount of change in condylar change. This study was aimed to evaluate the changes in condylar position when severe anterior open bite patients were treated with MEAW. The subjects consisted of 11 patients(21 TMJs) who visited the departement of orthodontics in SNUH, having severe anterior open bite as a chief complain. They were supposed to wear the up and down elastics and MEAW after finishing the leveling. The condylar position was evaluated with individualized corrected tomography in centric occlusion taken before and after treatment. The results were as follows ; 1. In the change of condylar position after treatment, there were no statistically significant differences in right and left TMJs. 2. In the change of condylar position after treatment, there were no statistically significant differences in each malocclusion groups. 3. There were no statistically significant differences in percent dispacement of condyle between before and after treatment. 4. There were no statistically significant differences in the amount of change in condylar change.

Brain Topological Correlates of Motor Performance Changes After Repetitive Transcranial Magnetic Stimulation

Park, Chang-hyun,Chang, Won Hyuk,Yoo, Woo-Kyoung,Shin, Yong-Il,Kim, Sung Tae,Kim, Yun-Hee Mary Ann Liebert 2014 Brain connectivity Vol.4 No.4

<P>Repetitive transcranial magnetic stimulation (rTMS) influences the brain temporally beyond the stimulation period and spatially beyond the stimulation site. Application of rTMS over the primary motor cortex (M1) has been shown to lead to plastic changes in interregional connectivity over the motor system as well as alterations in motor performance. With a sequential combination of rTMS over the M1 and functional magnetic resonance imaging (fMRI), we sought changes in the topology of brain networks and specifically the association of brain topological changes with motor performance changes. In a sham-controlled parallel group experimental design, real or sham rTMS was administered to each of the 15 healthy subjects without prior motor-related dysfunctions, over the right M1 at a high frequency of 10 Hz. Before and after the intervention, fMRI data were acquired during a sequential finger motor task using the left, nondominant hand. Changes in the topology of brain networks were assessed in terms of global and local efficiency, which measures the efficiency in transporting information at global and local scales, respectively, provided by graph-theoretical analysis. Greater motor performance changes toward improvements after real rTMS were shown in individuals who exhibited more increases in global efficiency and more decreases in local efficiency. The enhancement of motor performance after rTMS is supposed to be associated with brain topological changes, such that global information exchange is facilitated, while local information exchange is restricted.</P>

최빈국 지역정부의 기후변화적응계획 수립을 위한 기술적 가이드라인 개발 연구

장훈 ( Hoon Chang ),송영일 ( Young-il Song ),심창섭,문지원,이명주 한국환경정책평가연구원 2016 기후환경정책연구 Vol.2016 No.-

전 세계적으로 기후변화가 가속화됨에 따라 이로 인한 영향과 피해가 더욱 심각해지고 있다. 선진국보다는 최빈국이 기후변화에 의한 위험에 더욱 취약함에 따라 유엔기후변화협약에서 는 최빈국을 대상으로 기후변화로 인한 피해 저감을 위하여 기후변화적응계획 수립을 권고하였다. 유엔개발계획, 유엔기후변화협약 등의 국제기구 혹은 몇몇 국가에서는 기후변화적응계획 수립 가이드라인을 마련하여 최빈국의 적응계획 수립을 지원하고 있으나 현재까지 적응계획의 수립은 저조한 상황이다. 2010년 COP16에서부터 기후변화적응계획 수립을 권고하였으나 48개 최빈국 중 현재까지 다섯 국가에서만 적응계획 수립을 완료하였다. 한편 유엔자본 개발기금5)에서는 최빈국 지자체의 기후변화적응 능력 향상을 위해 LoCAL 프로젝트를 추진하고 있으며, KEI는 국내에서의 기후변화적응계획 수립 노하우를 토대로 동 프로젝트에 기술적 측면의 지원을 하고 있다. 이러한 KEI 지원의 일환으로 본 연구에서는 최빈국 지역정부의 기후변화적응계획 수립을 위한 가이드라인을 개발하고 이를 최빈국 중 하나인 부탄에 적용하였다. 본 연구에서 제안하는 가이드라인의 세부적인 내용은 다음과 같다. 중앙정부뿐만 아니라 지자체에서도 활용 가능하도록 국내외 기후변화적응계획 수립 관련 가이드라인을 검토하여, 절차별 방법이나 특성을 파악하였다. 그리고 부탄 및 캄보디아와 같은 일부 최빈국을 방문하여 현지 조사를 통해 가이드라인의 개발 방향을 정립하였다. 본 연구에서 제안하고 있는 기후변화적응계획 수립의 절차는 국내 기초지자체의 계획 수립 절차를 참고하였고, 절차별 과학적인 평가 방법은 필요한 자료의 유무나 질을 고려하여 정성적 또는 정량적 측면의 방법을 총 8단계로 나누어 제안하였다. 지역의 일반 현황과 기후변화 현황을 분석하고, RCP 시나리오 기반의 기후변화 전망을 분석하여 향후 기온이나 강수량이 기후변화로 인해 어떻게 변화하는지 예측하는 방법을 제안하였다. 그리고 이해당사자를 대상으로 기후변화적응에 대한 니즈를 파악하여 우선적으로 고려해야 할 사항이 무엇인지 판단하고, 과거 구축된 자료를 바탕으로 기후변화로 인한 재해 및 영향이 무엇인지 분석하는 방안을 제안 하였다. 취약성 평가는 수행 여건에 따라 정량적, 정성적 방법으로 평가될 수 있으며, 리스크는 3회에 걸친 전문가 설문을 통해 정성적인 방법으로 분석하도록 하였다. 이와 같이 분석된 종합적인 평가 결과를 기존의 최빈국 개발사업(investment menu)과 비교하여 적응계획 이행을 위하여 우선적으로 추진해야 할 사업을 선정하고, 체계적인 평가 및 모니터링 전략을 구축하는 등 전반적인 적응계획 수립 및 이행에 걸친 방안을 제안하였다. Due to accelerated climate change, its impacts and devastations are increasing day by day. As developing countries are more vulnerable to climate change compared to developed countries, UNFCCC recommended the development of a climate change adaptation plan in order to reduce their exposure to risks derived by climate change. Since COP 16, 2010, developing countries were encouraged to establish National Adaptation Plans(NAPs). Including UNDP and UNFCCC, many organizations proposed guidelines to assist the development of NAPs. yet only 5 out of 49 countries have officially submitted them. Meanwhile, UNCDF has been supporting the developing countries to foster their climate change adaptation capacities through LoCAL projects, while the Korea Environment Institute(KEI) has been providing technical elements for the projects. In alignment to such activities, this research have employed the guideline for the formation of the adaptation plans for local governments in Bhutan as a pilot program. The guideline is comprised by the study of various climate change adaptation planning guidelines and its attributes of each procedures. As case studies, field missions were carried out in Bhutan and Cambodia to enhance the understanding of the research. In regards of the process on composing the National Adaptation Plans, this research referred to the Korean national adaptation plans of the local governments. In consideration of the availability and quality of statistical information, the scientific procedures has been comprised in eight qualitative and qualitative steps. Through the analysis of the region`s general circumstances, climatic factors and RCP based scenario examinations, this research presents how to estimate the shift of temperature and precipitation altered by climate change. Moreover it raises the necessity of the needs of climate change adaptation to be prioritized through stakeholders and added on to the accumulated data and reviewed in the aspects of climate change disasters. For the vulnerability assessment, depending on the circumstances, both qualitative and quantitative methods may be applied and the risk evaluation will be conducted by three stages of expert surveys. The outcome derived by such methodologies will be assessed with prior LDC investment menus and considered when selecting the priority projects for initiating the adaptation plans.

Long second toe: its nail and skin changes

( Geun-hwi Park ),( Woo-il Kim ),( Min-young Yang ),( Won-ku Lee ),( Tae-wook Kim ),( Sung-min Park ),( Hyun-joo Lee ),( Gun-wook Kim ),( Hoon-soo Kim ),( Hyun-chang Ko ),( Byung-soo Kim ),( Moon-bum 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

Background: Nail can be affected by trauma, infection, and systematic disorders. In particular, the toe nails are exposed to the repeated and cumulative minor traumas, which usually result in thickened, splitted, and discolorated nails. Considering these, it can be inferred that the long second toe can be related to various nail and skin changes by repeated minor traumas such as friction in shoes, but the study or report on this topic hasn’t been done yet. Objectives: The purpose of this study was to introduce various nail and skin changes on long second toe. Methods: We analyzed the kinds of nail/skin changes of 50 patients with long second toe, enrolled at Pusan National University Hospitals (Busan and Yangsan) from 2013 to 2018. Results: There was no significant difference in the incidence of left and right toe and toenail, and 7 (14%) patients presented bilateral distribution. The most common nail change on long second toe was melanonychia (23, 46%), followed by subungual hematoma (15, 30%), onycholysis (2, 4%), subungual hyperkeratosis (2, 4%), onychomadesis (1, 2%), and retronychia (1, 2%). The most common skin change was corn (9, 18%), followed by paronychia (2, 4%). Twenty (20/50, 40%) patients also had other toe or toenail changes. Among them, the most common site was big toe/nail (13, 62%), and the most common change was subungual hematoma (8, 42%). Conclusion: Through this study, the dermatologists can recognize and diagnose the nail and skin changes of long second toe.

The Correlation of Serum IL-12B Expression With Disease Activity in Patients With Inflammatory Bowel Disease

Lee, Hye Won,Chung, Sook Hee,Moon, Chang Mo,Che, Xiumei,Kim, Seung Won,Park, Soo Jung,Hong, Sung Pil,Kim, Tae Il,Kim, Won Ho,Cheon, Jae Hee Williams & Wilkins Co 2016 Medicine Vol.95 No.23

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>Genetic variants in <I>IL12B</I>, encoding the p40 subunit common in interleukin-12 (IL-12) and interleukin-23, were identified as the susceptibility loci for inflammatory bowel disease (IBD). This study aimed to identify the correlation of serum IL-12B expression with disease activity in patients with IBD and evaluate the possibility of IL-12B as a biomarker for assessing inflammatory status in IBD.</P><P>A total of 102 patients with IBD, including 38, 32, and 32 patients with Crohn's disease (CD), ulcerative colitis (UC), and intestinal Behçet's disease (intestinal BD), respectively, were included. The clinical and laboratory data from the patients were collected at the time of serum IL-12B measurement. Serum IL-12B levels were measured using an enzyme-linked immunosorbent assay.</P><P>The median IL-12B levels in patients with CD, UC, and intestinal BD were significantly higher than those in controls (1.87, 2.74, and 2.73 pg/mL, respectively, vs. 1.42 pg/mL, all <I>P</I> <0.05). IL-12B concentrations were associated with disease activity in patients with UC and intestinal BD but not in those with CD. IL-12B levels were increased with increasing disease activity in patients with UC (<I>P</I> <0.001). Likewise, patients with active intestinal BD had higher IL-12B levels than those without active disease (<I>P</I> = 0.008). IL-12B levels were correlated with the endoscopic disease activity of UC (<I>P</I> = 0.002) and intestinal BD (<I>P</I> = 0.001) but not that of CD.</P><P>Serum IL-12B levels were significantly correlated with clinical and endoscopic disease activity in patients with UC and intestinal BD, suggesting its potential use as a biomarker for assessing disease activity in these patients.</P></▼2>

Genetic effect of <i>CCR3</i> and <i>IL5RA</i> gene polymorphisms on eosinophilia in asthmatic patients

Lee, June-Hyuk,Chang, Hun Soo,Kim, Ji Hyun,Park, Se-Min,Lee, Yong Mok,Uh, Soo Taek,Rhim, Taiyoun,Chung, Il Yup,Kim, Yong-Hoon,Park, Byung Lae,Park, Choon-Sik,Shin, Hyoung Doo Elsevier 2007 The journal of allergy and clinical immunology Vol.120 No.5

<P><B>Background</B></P><P>Eosinophilic infiltration and peripheral blood eosinophilia in asthma require the cooperation of eosinophil-specific cytokines and chemokines and their receptors.</P><P><B>Objective</B></P><P>We investigated the association of polymorphisms in <I>CCR3</I> and <I>IL5RA</I> with asthma susceptibility or peripheral blood eosinophilia and the effects of the polymorphisms on receptor expression.</P><P><B>Methods</B></P><P>Polymorphisms in <I>CCR3</I> and <I>IL5RA</I> were identified and genotyped in 576 asthmatic patients and 180 healthy control subjects. CCR3 and IL-5 receptor α (IL-5Rα) protein expression on eosinophils was measured by means of flow cytometry.</P><P><B>Results</B></P><P>Although polymorphisms in <I>CCR3</I> were not associated with asthma susceptibility, the <I>CCR3</I> haplotype <I>ht2</I> showed a negative gene dose effect on the eosinophil count (<I>P</I> = .003–.009). <I>IL5RA c.−5091G>A</I> was weakly associated with eosinophil count. The effects of <I>ht2</I> were greater when paired with <I>IL5RA c.−5091A</I> (<I>P</I> = .001–.002). CCR3 protein expression was higher on eosinophils of asthmatic patients without <I>ht2</I> than in those with <I>ht2</I>. Asthmatic patients with the <I>IL5RA c.−5091A</I> allele showed higher IL-5Rα expression than those who were homozygous for the G allele.</P><P><B>Conclusion</B></P><P>The genetic association between <I>CCR3</I> polymorphisms and the number of circulating eosinophils was revealed as a novel finding. These associations were more pronounced when the <I>CCR3</I> polymorphisms were paired with polymorphisms in <I>IL5RA</I>. The protein expression levels of CCR3 and IL-5Rα on peripheral blood eosinophils are associated with the polymorphisms on their own genes.</P><P><B>Clinical implications</B></P><P>The identification of single nucleotide polymorphisms and haplotypes of <I>CCR3</I> and <I>IL5RA</I> might be useful in developing markers for intermediate phenotypes of eosinophil number and in designing strategies to control diseases related to hypereosinophilia.</P>

퇴행성 관절염에서 Interleukin-6와 Soluble Interleukin-6 Receptor

장재석 ( Jae Suk Chang ),정용갑 ( Yong Gab Jeong ),조우신 ( Woo Shin Cho ),빈성일 ( Seong Il Bin ),엄규황 ( Kyu Hwang Ym ),김정화 ( Jung Hwa Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.3

Objective: Unlike other soluble receptors, the soluble interleukin-6 receptor (sIL-6R) cooperates with IL-6 to activate gp130 of effector cell. As the IL-6 and sIL-6R are important in the rheumatoid disease, this study was designed to measure concentration of IL-6 and sIL-6R in synovium and synovial fluid of the degenerative arthritis. Methods: The synovium and synovial fluid were obtained during total knee replacement arthroplasty. The synovium was taken from eleven patients, and synovial fluid taken from sixteen patients. Same patients between two groups were seven. Tissue cultures of the synovial tissues were done with 10% FBS for 72 hours. After irrigation, thery were incubated for 48 hours without FBS, and the culture media and the synovial fluid were collected after centrifuged at 2500rpm for 10 minutes. The level of IL-6 and sIL-6R were measured by quantitative sandwich enzyme immunoassay technique. Results: In the synovium, the IL-6 level was 5.1±0.12ng/ml, and the sIL-6R level was 0.41±0.25ng/ml. In the synovial fluid, the IL-6 level was 0.09± 0.15ng/ml, and the sIL-6R level was 10.37±3.28ng/ml. These results show that IL-6 concentration was measured highly in two groups, especially in synovium (sixty times), and the sIL-6R concentration was measured significantly high in synovial fluid (twenty-five times). Conclusion: The IL-6 and sIL-6R were elevated in degenerative arthrits. We confirmed the source of IL-6 was synovium (very high in synovial tissue culture media), but we need further study for the source of sIL-6R as it was remarkably elevated as IL-6 and its level was lower than serum.

Blockade of indoleamine 2,3-dioxygenase protects mice against lipopolysaccharide-induced endotoxin shock.

Jung, In Duk,Lee, Min-Goo,Chang, Jeong Hyun,Lee, Jun Sik,Jeong, Young-Il,Lee, Chang-Min,Park, Won Sun,Han, Jin,Seo, Su-Kil,Lee, Sang Yong,Park, Yeong-Min Williams Wilkins 2009 JOURNAL OF IMMUNOLOGY Vol.182 No.5

<P>Suppression of an excessive systemic inflammatory response is a promising and potent strategy for treating endotoxic sepsis. Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan catabolism, may play a critical role in various inflammatory disorders. In this study, we report a critical role for IDO in the dysregulated immune response associated with endotoxin shock. We found that IDO knockout (IDO(-/-)) mice and 1-methyl-D-tryptophan-treated, endotoxin-shocked mice had decreased levels of the cytokines, TNF-alpha, IL-6, and IL-12, and enhanced levels of IL-10. Blockade of IDO is thought to promote host survival in LPS-induced endotoxin shock, yet little is known about the molecular mechanisms that regulate IDO expression during endotoxin shock. In vitro and in vivo, IDO expression was increased by exogenous IL-12, but decreased by exogenous IL-10 in dendritic cells and splenic dendritic cells. Interestingly, whereas LPS-induced IL-12 levels in serum were higher than those of IL-10, the balance between serum IL-12 and IL-10 following challenge became reversed in IDO(-/-)- or 1-methyl-D-tryptophan-treated mice. Our findings demonstrate that the detrimental immune response to endotoxin shock may occur via IDO modulation. Restoring the IL-12 and IL-10 balance by blocking IDO represents a potential strategy for sepsis treatment.</P>