Interleukin-6 and Interleukin-10 in experimentally induced rat Pulpal inflammation

Chang, Seok-Woo,Baek, Seung-Ho,Kim, Chul-Ho,Lim, Sung-Sam 大韓齒科保存學會 2002 Restorative Dentistry & Endodontics Vol.27 No.3

연구목적 Cytokine은 유해 미생물에 대한 숙주의 방어기전으로서의 염증반응에서 숙주세포 상호간의 작용을 매개해 주는 역할을 하며, 인간의 치수조직에서도 그 존재가 확인된 바 있다. Interleukin-6와 Interleukin-10은 염증의 초기에 작용하는 cytokine으로 알려져 있으나, 수 및 치근단 질환에서의 역할과 상호작용에 대해서는 잘 알려져 있지 않다. 본 연구에서는 치수염의 원인균으로 알려진 Prevotella nigrescens를 이용하여 백서의 치수염을 유도한 후 시간의 변화에 따른 Interleukin-6, Interleukin-10의 농도의 변화를 측정하여 이들의 치수염에서의 작용을 알아보는 것을 목적으로 한다. 방법 실험적으로 치수의 염증반응을 일으키기 위하여 치수염의 원인균으로 알려진 Prevotella nigrescens를 이용하였다. 실험동물의 하악절치의 incisal tip부분을 절단한 후(n=120), 치수강을 개방시켰다. 실험군에서는 Prevotella nigrescens를 멸균된 면구에 묻혀서 개방된 치수강 내에 접종하였으며, 대조군에서는 균을 접종하지 않고 멸균된 면구만을 개방된 치수강 내에 위치시켰다. 그 후 1, 2, 5일이 경과되었을 때 실험에 사용된 치아를 발치하여, 치수조직을 적출하였다. Amersham사의 ELISA kit를 사용하여 적출된 치수조직내의 Interleukine-6와 Interleukine-10의 양을 측정하였으며 그 결과를 Mann-whitney rank sum test를 사용하여 통계학적 유의성을 검증하였다. 조직학적 검사를 위해서는 발치된 치아를 nitric acid를 사용하여 탈회시킨 후 헤마톡실린-에오신 염색을 시행한 후 관찰하였다. 결과 1) Interleukine-6의 농도는 균접종 후 1일, 2일, 5일 모두에서 실험군에서 대조군보다 높게 나타났으며, 균접종 1일째의 결과는 통계적 유의성이 있었다(P<0.05). 2) Interleukine-10의 농도는 균접종 후 1일, 2일, 5일 모두에서 실험군에서 대조군보다 높게 나타났으며, 균접종 1일째의 결과는 통계적 유의성이 있었다(P<0.05). 3) Interleukin-10/Interleukin-6 ratio는 실험군과 대조군 모두에서 1일보다 2일째의 결과에서 더 shb은 값을 보였으며 대조군에서는 통계적 유의성을 보였다(P<0.05). 4) 조직학적 관찰결과 균접종 후 2일째의 조직표본에서는 림프구의 침윤과 부분적인 조직의 괴사 등 염증반응의 양상을 관찰할 수 있었으며, 균접종 5일째의 조직표본에서는 염증의 정도가 감소되는 양상을 확인할 수 있었다.

Interleukin-10 이 $interleukin-1{\beta}$로 유도되는 골흡수에 미치는 효과

유윤정,강윤선,이승일,Yu, Yun-Jung,Kang, Yun-Sun,Lee, Syng-Ill 대한치주과학회 1994 Journal of Periodontal & Implant Science Vol.24 No.2

The cytokines released by osteoblasts induce bone resorption via the differentiation of osteoclast precursors. In this process, $interleukin-1{\beta}$($IL-1{\beta}$)-induced bone resorption is mediated by granulocyte macrophage-colony stimulation factor(GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor ${\alpha}$($TNF-{\alpha}$) released from osteoblasts. Since these cytokines (GM-CSF, IL-6, $TNF-{\alpha}$) are produced by not only osteoblasts but also monocytes, and interleukin-10(I1-10) inhibits the secretion of these cytokines from monocytes, it may be speculated that IL 10 could modulate the production of GM-CSF, IL-6, and $TNF-{\alpha}$ by osteoblasts, then control $IL-1{\beta}-induced$ bone resorption. Therefore, the aims of the present study were to examine the effects of IL-10 on bone resorption. The sixten or seventeen-day pregnant ICR mice were injected with $^{45}Ca$ and sacrificed one day after injection. Then fetal mouse calvaria prelabeled with $^{45}Ca$ were dissected out. In order to confirm the degree of bone resorption, mouse calvaria were treated with Lipopolysaccharide(LPS), $TNF-{\alpha}$, $IL-1{\alpha}$, IL-8, $IL-1{\beta}$, and $IL-1{\alpha}$, Then, IL-10 and $interferon-{\gamma}$ ($IFN-{\gamma}$) were added to calvarial medium, in an attempt to evaluate the effect of $IL-1{\beta}-induced$ bone resorption. In addition, osteoclasts formation in bone marrow cell cultures, and the concentration of IL-6, $TNF-{\alpha}$, and GM-CSF produced from mouse calvarial cells were investigated in response to $IL-1{\beta}$ alone and simultaneously adding f $IL-1{\beta}$ and IL-10. The degree of bone resorption was expressed as the ratio of $^{45}Ca$ release(the treated/the control). The osteoclasts in bone marrow cultures were indentified by tartrate resistant acid phosphatase(TRAP) stain and the concentration of the cytokines was quantified using enzyme linked immunosorbent method. As results of these studies, bone resorption was induced by LPS(1 ng/ml ; the ratio of $^{45}Ca$ release, $1.14{\pm}0.07$). Also $IL-1{\beta}$(1 ng/ml), $IL-1{\alpha}$(1 ng/ml), and $TNF-{\alpha}$(1 ng/ml) resulted in bone resorption(the rations of $^{45}Ca$ release, $1.61{\pm}0.26$, $1.77{\pm}0.03$, $1.20{\pm}0.15$ respectively), but IL-8 did not(the ratio of $^{45}Ca$ release, $0.93{\pm}0.21$). The ratios of $^{45}Ca$ release in response to IL-10(400 ng/ml) and $IFN-{\gamma}$(100 ng/ml) were $1.24{\pm}0.12$ and $1.08{\pm}0.04$ respectively, hence these cytokines inhibited $IL-1{\beta}$(1 ng/ml)-induced bone resorption(the ratio of $^{45}Ca$ release $1.65{\pm}0.24$). While $IL-1{\beta}$(1 ng/ml) increased the number of TRAP positive multinulcleated cells in bone marrow cultures($20{\pm}11$), simultaneously adding $IL-1{\beta}$(1 ng/ml) and IL-10(400 ng/ml) decreased the number of these cells($2{\pm}2$). Nevertheless, IL-10(400 ng/ml) did not affect the IL-6, GM-CSF, and $TNF-{\alpha}$ secretion from $IL-1{\beta}$(1 ng/ml)-activated mouse calvarial cells. From the above results, it may be suggested that IL-10 inhibites $IL-1{\beta}-induced$ osteoclast differntiation and bone resorption. However, the inhibitory effect of IL-10 on the osteoclast formation seems to be mediated not by the reduction of IL-6, GM-CSF, and $TNF-{\alpha}$ production, but by other mechanisms.

The role of Interleukin-6 and Interleukin-10 in human pulpal inflammation

Park, Han-Soo 大韓齒科保存學會 2002 Restorative Dentistry & Endodontics Vol.27 No.5

연구목적 Cytokine은 유해 미생물에 대한 숙주의 방어기간으로서의 염증반응에서 숙주세포 상호간의 작용을 매개해 주는 역할을 하며, 치수조직에서도 그 존재가 확인된 바 있다. Interleukin-6와 Interleukin-10은 염증의 초기에 작용하는 cytokine으로 알려져 있으나, 치수 및 치근단 질환에서의 역할과 상호작용에 대해서는 잘 알려져 있지 않다. 본 연구에서는 성인의 치수염이 있는 치아에서 Interleukin-6와 Interleukine-10의 농도를 측정하고 이를 정상 치수와 비교함으로써 이들의 치수염에서의 작용을 연구하는 것을 목적으로 하였다. 방법 총 60개의 성인 치아들을 대상으로 하였다. 치수염으로 진단된 치아들을 실험군들로 하였고, 정상 치수를 가진 치아들을 대조군으로 하였다. 발치한 치아에서 치수조직을 적출하였다. ELISA를 사용하여 적출된 치수조직 내의 Interleukin-6와 Interleukin-10의 양을 측정하였으며, 그 결과를 Mann-Whitney rank sum test를 사용하여 통계학적 유의성을 검증하였다. 조직학적 검사를 위해서는 발치된 치아에서 치수조직을 적출하여 헤마톡실린-에오신 염색을 시행한 후 관찰하였다. 결과 1. Interleukin-6의 농도는 실험군에서 대조군보다 유의하게 높게 나타났다.(p < 0.05). 2. Interleukin-10의 농도는 실험군에서 대조군보다 유의하게 높게 나타났다(p < 0.05). 3. 조직학적 관찰 결과 실험군에서 림프구의 침윤과 부분적인 조직의 괴사 등 염증반응의 양상을 관찰할 수 있었다.

Investigation of Interleukin-10 Promoter Polymorphisms and Interleukin-10 Levels in Children with Irritable Bowel Syndrome

( Man Chin Hua ),( Hsun Chin Chao ),( Tsung Chieh Yao ),( Ming Wei Lai ),( Jing Long Huang ),( The Patch Study Group ) 대한소화기학회 2013 Gut and Liver Vol.7 No.4

Background/Aims: The aim of this study was to investigate whether genetic variations at positions -1082, -819, and 592 in the interleukin (IL)-10 promoter affect IL-10 production in children with irritable bowel syndrome (IBS). Methods: Ninety-four children with IBS and 102 children as healthy controls (HCs) were enrolled. Genomic DNA was extracted, and IL-10 -1082, -819, and -592 polymorphisms were detected by direct sequencing from all participants. Peripheral blood mononuclear cells (PBMCs) from 46 IBS children and 38 HCs were isolated and cultured with and without 5 ng/mL Escherichia coli lipopolysaccharide (LPS). IL-10 levels in the culture supernatants were measured by enzyme-linked immunosorbent assay. Results: There were no significant differences in the distribution of IL-10 -1082, -819, and -592 polymorphisms or in the allele and haplotype frequencies between IBS children and HCs. PBMCs from children with IBS had significantly lower IL-10 levels after LPS stimulation than PBMCs from HCs (p=0.011); however, LPS-induced IL-10 levels in PBMCs with different genotypes of -819 and 592 polymorphisms were not significantly different between IBS patients and HCs. Conclusions: Although significantly lower LPS-induced IL-10 production by PBMCs was noted, it is unlikely that IL-10 production was fully genetically determined in our IBS children. ClinicalTrials.gov identifier: NCT01131442. (Gut Liver 2013; 7:430-436)

한국인 신이식 환자에서 Interleukin-10과 Interferon-γ의 유전자 다형성이 이식신의 임상경과에 미치는 영향

박성훈 ( Sung Hoon Purk ),강기주 ( Ki Joo Kang ),송영림 ( Young Rim Song ),채동완 ( Dong Wan Chae ),오국환 ( Kook Hwan Oh ),김성균 ( Seong Gyun Kim ),노정우 ( Jung Woo Noh ),이영기 ( Young Ki Lee ),임춘수 ( Chun Su Lim ),김연수 ( 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.6

목 적 : Interleukin-10 (IL-10) 유전자 프로모터 (promoter)에 존재하는 3가지 단일 염기 다형성 (aingle nucleotide polymorphism : SNP)과 Interferon-γ (INF-γ) 유전자 첫 번째 인트론의 allele*C와 *A의 병렬적 반복횟수의 다형성 (variable numbers of tandem repeat : VNTR)은 각각 mitogen 자극에 의한 IL-10과 IFN-γ의 생성량에 영향을 주는 것으로 보고되고 있다. INF-γ와 IL-10은 각각 주된 Th1과 Th2 사이토카인으로 이식항원에 대한 개체의 면역반응에 중요한 역할을 한다. 따라서 이식 환자의 유전적 다형성에 따른 이식항원에 대한 IFN-γ와 IL-10의 생성양의 차이는 이식신에 대한 면역반응의 차이를 유발하고 궁극적으로 이식신의 임상경과에 영향을 미치리라 판단된다. 이에 연구자들은 신이식 수술을 받은 한국인 환자에서 IFN-γ와 IL-10의 유전자 다형성을 조사하고, 이들 사이토카인의 유전적 다형성이 이식신의 임상적 경과에 미치는 영향을 파악하고자 본 연구를 시행하였다. 방 법 : 1991년부터 2000년까지 강동성심병원에서 신이식 수술을 받고 5개월 이상 추적 관찰된 185명의 환자와 혈압이 정상이고 병력 및 검사소견에서 신질환의 증거가 없는 98명의 대조군을 대상으로 하였다. PCR과 특정 제한효소를 이용한 PCR -RFLP의 방법으로 IL-10 promoter의 세 가지의 SNP를 조사하였고, IFN-γ 유전자 첫 번째 인트론에 존재하는 CA 염기의 VNTR은 PCR 생성물의 크기에 따라 측정하였다. 유전적 다형성과 이식 환자의 임상적 경과의 관련성은 Chi-square test와 fisher`s Exact test 및 student t-test를 이용하여 평가하였다. 결 과 : IFN-γ에서는 신이식 환자와 대조군간의 allele*2와 allele*3의 분포의 차이는 없었다. 모든 연구 대상에서 IL-10 promoter의 전사시작부위에서 -592 위치의 allele*A와 *C은 각각 -819 위치의 allele*T와 *C과 연관 (ilnkeage)되었다. -1,082 위치의 *C/*A genotype은 신이식 환자에서 7.0%로 대조군의 17.3%에 비하여 낮았다(p=0.02). *C/*G genotype은 모든 대상 환자에서 관찰되지 않았다. IL-10와 IFN-γ의 유전적 다형성은 급성거부반응의 빈도나 중증조와는 관련이 없었고, 추적 관찰기간 중 혈청 크레아티닌 농도의 증가에도 영향을 주지 않았다. 결 론 : 한국인의 IFN-γ첫 번째 intron의 VNTR 다형성의 분포는 서양인에서의 보고와 유사하였으나 IL-10 promotor SNP 다형성은 서양인과 대단히 상이한 분포가 관찰되었고 -1,082 *G/*A genotype의 빈도가 신이식 환자에서 대조군에 비하여 낮았다. 한국인에서의 IL-10와 IFN-γ의 유전적 다형성은 이식신의 임상적 경과에 의미있는 영향을 주지 못하였다. Background : The single nucleotide polymorphism (SNP) of interleukin-10 and the variable number of tandem repeat (VNTR) of CA dinucleotide of Interferon-γ are reported to have an influence on the production of IL-10 and IFN-γ respectively. The aims of this study are to investigate the gene polymorphisms of IL-10 and IFN-γ in Korean renal transplant patients and to assess their impacts on the clinical courses of renal allografts. Methods : The one hundred eighty-five patients who received renal allografts and were followed for more than 5 months from 1991 to May 2000 in Kangdong Sacred Heart Hospital, and ninety-eight normal healty controls were investigated, Three SNPs in promoter region of IL-10 gene were assayed by PCR-RFLP. The (CA) dinucleotide repeat polymorphism of IFN-γwere assessed by evaluation of size of PCR products. Results : Allele*2 and allele*3 were major alleles of IFN-γ in our study and there was no significant difference of alleleic and genotypic distribution between recipient and control group. The -592*A and -592*C in the IL-10 promotor region were tightly linded to -819*T and -819*C, respectively. The frequency of -1082*G/*A genotype of recipent group was 7.0% and smaller than that of control group (17.3%, p=0.02). The *G/*G genotype (IL-10 high producer) was absent in all our study subjects, which was quite different from Western studies. IFN-7 and IL-10 gene polymorphisms had no impact on the incidence and severity of acute rejection, and long term graft fucntion after transplantation. Conclusion. Unlike IFN-γ the SNPs of IL-10 promoter were qua different from those in Western patients. The frequency of -1,082*G/*A genotype of IL-10 was smaller in recipient group. In conclusion, the polymorphisms of IL-10 and IFN-γ had no impact on the clinical courses of renal allografts under the current therapeutic strategies.

Effect of Cyclosporine on Circulating Interleukin-10 and Interleukin-12 in Pateints with Severe, Refractory Rheumatoid Arthritis

Kim, Jeong-Sun,Kim, Wan-Uk,Cho, Mi-La,Youn, Jee-Hee,Lee, Suk-Kyeong,Chae, Eun-Young,Min, Jun-Ki,Hong, Yeon-Sik,Lee, Sang-Heon,Park, Sung-Hwan,Cho, Chul-Soo,Kim, Ho-Youn 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

Background : To investigate the effect of cyclosporine on interleukin-10 (IL-10) and interleukin-12 (IL-12) in patients with rheumatoid arthrtis (RA) Methods : A 10-week randomized, double blind, placebo-control study of cyclosporine RA who had residual inflammation and isability despite partial reponses to prior maximal tolerated dose of methotrexate (<15 mg/week) and low dose prednisone (<10 mg/day). The clinical and laboratory variables, and circulating leves IL-10 and IL-12 measered by enzymelinked immunosorbent method, were compared between patients (cyclosporine group) treated with cycloporine plus methotreaxte and those (placebo group) treated with placebo plus methotrexate at the entry and 16 weeks of the study. Results : On the 16 weeks into the clinical trial, the cyclosporine group (n=17), compared with the placebo group (n=17), had higher degree of decreases in tender joints, patients global assessment, patients self assessed disability, C-reactive protein as well as having more patients with over 20% improvement. The comparison of the circulating IL-10 and IL-12 at the entry and 16 weeks of the study showed significant decreases of IL-12(median-313 versrs -14 pg/ml, p=0.002) and a significant increase of IL-10 (median 55 versus-12 pg/ml, p <0.001) in the cyclosporine group compared with the placebo group. The degree of IL-10 increases strongly correlated with the degree of IL-12 decreases in the cyclosporine group (r=0.572, p=0.016). Among the cyclosporine group, the improved patients (n 10), compared to the non-improved patients (n=7), had higher rate of increase in the circulating IL-10 (median 172.0 versus 85.2%, p=0.01). The rate of increase of IL-10 strongly correlated with the rate of improvement of joint scores (r=0.718, p=0.001) after administration of cyclosporine. Conclusion : Our results suggest that the therapeuic effect of cyclosporine is achieved by correcting Th1/Th2 imbalance (a shift Th1 type to Th2 type), which may be in the pathogenesis of RA, and circulating IL-10 is useful to assess the clinical improvements in patients with RA after administration of cyclosporine. (Korean Journal of BRM 9(1):19-30, 1999)

Vibrio vulnificus cytolysin 독혈증의 정도에 따른 TNF-α와 Interleukin 19치의 변화와 그 의의

전재훈(Jae Hoon Chun),차승훈(Seung Hoon Cha),박석돈(Seok Don Park) 대한피부과학회 2001 大韓皮膚科學會誌 Vol.39 No.6

N/A Background: Pro-inflammatory cytokines, such as tumor necrosis factor(TNF)-α and interleukin (IL)-1, have been incriminated in the pathogenesis of septic shock in animals and humans. IL-10 reduces the release of pro-inflammatory cytokines, nitric oxide and reactive oxygen species. IL-10 prevents endotoxin-induced toxicity. Objective : The aim of this study was to investigate the relation between IL-10 and TNF-α in toxemic mice according to concentrations of V. vulnificus cytolysin. Methods : First, after administration of V.vulnificus cytolysin(2, 4, 6, 8, 10 hemolytic units; HU) and physiologic saline through a mouse tail vein, we obtained blood samples from the heart at 60 minutes which was a peak time of IL-10 and TNF-a release. We measured serum concentration of circulating TNF-α and IL-10 using commercially available enzyme-linked immunosorbent assay methods. Second, after administration of 1,000U recombinant mouse IL-10 through a mouse tail vein 30 min before infusion of the lethal dose(8HU) of V. vulnificus cytolysin. We obtained blood samples from the heart at 60 minutes and measured serum concentration of circulating TNF-α level. Results : Both IL-10 and TNF-α levels were significantly correlated with V. vulnificus cytolysin concentration(P 0.002). TNF-α levels were 76.9±9.5 pg/㎖ in 2HU, 315.8±39.8 pg/㎖ in 4HU, 426.1±27.9 pg/㎖ in 6HU, 931.3±22.3 pg/㎖ in 8HU, 1825.2±18.8 pg/㎖ in 10HU and 23.6±5.1 pg/㎖ in physiologic saline. IL-10 levels were 80.2±21.5 pg/㎖ in 2HU, 244.4±35.4 pg/㎖ in 4HU, 382.2±22.6 pg/㎖ in 6HU, 740.1±33.0 pg/㎖ in 8HU, 997.3±16.8 pg/㎖ in 10HU and 35.8±15.0 pg/㎖ in physiologic saline. After administration of 1,000U recombinant mouse IL-10, comparing to control group(931.3±22.3 pg/㎖), TNF- a level was reduced to 307.2±23.9 pg/㎖(P 0.003). Conclusion: IL-10 has an inhibitory effect on the production of TNF-α although it is released together with TNF-α in toxemic mice. IL-10 blood levels are directly related to the severity of toxemia. We conclude that IL-10 is a prognostic factor for the development of sepsis and might be used for the treatment of sepsis. (Korean J Dermatol 2001;39(6): 643~647)

백서의 콜라겐 유도성 관절염 발생에 미치는 Interleukin-10의 영향

유빈 ( Bin Yoo ),김찬 ( Chan Kim ),최승원 ( Seung Won Choi ),김미정 ( Mi Jung Kim ),오순환 ( Sun Whan Oh ),문희범 ( Hee Bom Moon ) 대한류마티스학회 1997 대한류마티스학회지 Vol.4 No.2

콜라겐 유도성 관절염을 발생시키는 과정에서 IL-10을 투여한 본 연구에서는 관절염을 악화시키는 결과를 보였다. 이는 시험관내 실험상 염증억제효과뿐만 아니라 여러 면역세포 촉진 작용도 보인다고 알려진 IL-10이 본 연구에서의 용량으로 콜라겐 항원자극시부터 CIA 모델에 투여하면 관절염의 악화 효과를 보일 수 있음을 보여주었다. 관절염의 중증도나 IL-10투여와 무관하게 콜라겐항체 농도나 비장세포 자극지수가 증가함은 관절염의 악화에 콜라겐항체나 콜라겐 특이 반응세포의 역할외에 다른 기전의 역할임을 알 수 있었다. 본 연구 결과와 상반된 관찰을 보고한 다른 실험의 방법과 본 연구방법의 차이점을 고려할 때 IL-10은 다른 생물학적 제제들과 유사한 속성으로 작용 시기와 용량에 따라서 서로 다른 작용을 보일 가능성을 시사하였다. IL-10이 CIA 발생을 악화시킬 수 있는 기전은 항원제시 세포로서의 B 림프구의 자극, 세포독성 T 림프구의 자극, 대식세포로부터의 산화질소 생성 촉진 등이 가능하나 그 정확한 기전은 향후 더 연구되어야 할 과제라 생각된다. Objective: To evaluate the effect of IL-10 on development of collagen-induced arthritis, on humoral and cellular immunity and on the endogenous production of IL-10 in DBA/1J mice. Methods: DBA/1J mice were immunized with chicken type II collagen in Freund`s complete adjuvant. Murine recombinant IL-10 was given intraperitoneally twice a week from the day of second immunization (week 3) in doses of 0.002ug, 0.02ug and 0.2ug for 3 different groups, respectively. Dexamethasone was injected in one group to suppress the arthritis development and this group was used as negative control group. Levels of anti-collagen antibodies, serum IL-10 and stimulation indices of splenic monocytes to collagen were measured at the end of study. Results: The 0.02ug IL-10 and 0.2ug IL-10 treated groups developed earlier and more severe arthritis (week 6 and 8) compared to that of the control group while the 0.002ug IL-10 group has shown similar course to the control group in terms of incidence and severity of arthritis, At week 10, all groups with or without IL-10 injections developed arthritis with similar degree of severity while dexamethasone group showed far less incidence and severity of arthritis. The serum levels of anti-collagen antibody, IL-10 and spleen monocyte stimulation indices to collagen antigen showed no difference among control group, IL-10 injected groups and dexamethasone injected group. Conclusion: This study shows IL-10 could worsen the arthritis in CIA with the dosage used in this study without significant influence on the level of anti-collagen antibodies or stimulation indices of spenic monocyte to collagen.

A proinflammatory cytokine interleukin-32&bgr; promotes the production of an anti-inflammatory cytokine interleukin-10

Kang, Jeong-Woo,Choi, Seung-Chul,Cho, Min-Chul,Kim, Hee-Jong,Kim, Jae-Hwa,Lim, Jong-Seok,Kim, Soo-Hyun,Han, Jae-Yong,Yoon, Do-Young Blackwell Publishing Ltd 2009 Immunology Vol.128 No.1

<P>P>A new proinflammatory cytokine interleukin-32 (IL-32) has six isoforms. Although IL-32 can be detected in sera from patients suffering from Crohn's disease and rheumatoid arthritis, it is unclear which isoforms are involved. To this end, we investigated the functions of the most abundant IL-32 beta by generating K562-IL-32 beta stable cell lines. This report confirms, using IL-32 small interfering RNA, that IL-32 beta induces an anti-inflammatory cytokine IL-10 in K562-IL-32 beta cells and U937 promonocytic cells, which express endogenous IL-32 beta upon phorbol 12-myristate 13-acetate (PMA) treatment, and monocyte-derived dendritic cells (DC) upon lipopolysaccharide (LPS) treatment. Interleukin-32 beta was induced in monocyte-derived macrophages by LPS and in monocyte-derived DC by LPS, poly(I:C), or anti-CD40 antibody, but was not induced by PMA. We showed that IL-32 beta expression was increased in a time-dependent manner in monocyte-derived DC upon LPS treatment and peaked at 24 hr. Production of IL-10 was exactly coincident with IL-32 beta expression, but IL-1 beta and tumour necrosis factor-alpha production peaked at 6 hr after LPS treatment, then steeply declined. Interleukin-12 p40 was induced at 9 hr and gradually increased until 48 hr, at which time IL-32 beta and IL-10 were no longer increased. Knock-down of IL-32 beta by IL-32 small interfering RNA led to the decrease of IL-10, but the increase of IL-12 in monocyte-derived DC, which means that IL-32 beta promotes IL-10 production, but limits IL-12 production. We also showed that IL-10 neutralization increases IL-12, IL-1 beta and tumour necrosis factor-alpha production, which implies that IL-10 suppresses such proinflammatory cytokines. Taken together, our results suggest that IL-32 beta upregulates the production of an anti-inflammatory cytokine IL-10, and then IL-10 suppresses proinflammatory cytokines.</P>

심폐소생술 후 순환회복 되어 저체온 요법을 시행한 환자에서 신경학적 예후에 따른 혈청 Interleukin-6와 Interleukin-10의 발현 양상

정건영,이미진,양혁준,임용수,김진주,김재광,김정권,이형석 대한응급의학회 2009 大韓應急醫學會誌 Vol.20 No.1

Purpose: We wanted to investigate the serial changes of the serum interleukin-6 (IL-6) and interleukin-10 (IL-10) concentrations, according to the neurological outcome, in patients who received therapeutic hypothermia after successful cardiopulmonary resuscitation. We also wanted to evaluate the usefulness of serum IL-6 and IL-10 as biochemical markers to predict the neurological outcome. Methods: We prospectively evaluated 23 patients who received therapeutic hypothermia after successful cardiopulmonary resuscitation. Blood samples were taken at 0, 4, 12, 24 and 48 hours after the return of spontaneous circulation. We compared the IL-6 and IL-10 levels between the good (CPC 1 to 2) and poor (CPC 3 to 5) neurological outcome (NO) groups. Results: The serum IL-6 level at 0 hr was significantly higher in the good NO group than that in the poor NO group. The periods of time that showed the greatest pattern of change between the good and poor NO groups were 4-12 hr for the IL-6 level and 0-4 hr for the IL-10 level. On the analysis of the ROC curve, the cut-off value for delta IL-10 (0-4 hr) was -5.4 pg/ml (AUC=0.827, sensitivity 80.0%, specificity 93.3%, p=0.032) and the cut-off value for delta IL-6 (4-12 hr) was 62.8 ng/ml (AUC=0.527, sensitivity 80.0%, specificity 34.0%, p=0.861, respectively). Conclusion: Our study suggests that the early delta IL-10 can be used as a neurological prognostic marker for patients who are undergoing therapeutic hypothermia after successful cardiopulmonary resuscitation.