• IMMUNE NETWORK
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• 제24권1호
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• pp.1.1-1.6
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• 2024

IL-18 binding protein (IL-18BP) was originally discovered in 1999 while attempting to identify an IL-18 receptor ligand binding chain (also known as IL-18Rα) by subjecting concentrated human urine to an IL-18 ligand affinity column. The IL-18 ligand chromatography purified molecule was analyzed by protein microsequencing. The result revealed a novel 40 amino acid polypeptide. To isolate the complete open reading frame (ORF), various human and mouse cDNA libraries were screened using cDNA probe derived from the novel IL-18 affinity column bound molecule. The identified entire ORF gene was thought to be an IL-18Rα gene. However, IL-18BP has been proven to be a unique soluble antagonist that shares homology with a variety of viral proteins that are distinct from the IL-18Rα and IL-18Rβ chains. The IL-18BP cDNA was used to generate recombinant IL-18BP (rIL-18BP), which was indispensable for characterizing the role of IL-18BP in vitro and in vivo. Mammalian cell lines were used to produce rIL-18BP due to its glycosylation-dependent activity of IL-18BP (approximately 20 kDa). Various forms of rIL-18BP, intact, C-terminal his-tag, and Fc fusion proteins were produced for in vitro and in vivo experiments. Data showed potent neutralization of IL-18 activity, which seems promising for clinical application in immune diseases involving IL-18. However, it was a long journey from discovery to clinical use although there have been various clinical trials since IL-18BP was discovered in 1999. This review primarily covers the discovery of IL-18BP along with how basic research influences the clinical development of IL-18BP.

• Journal of Chest Surgery
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• 제33권8호
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• pp.648-654
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• 2000

Background: Cardiopulmonary bypass during open heart surgery causes systemic inflammatory respose. IL-10 is an anti-inflammatory cytokine that inhibits inflammatory process and protects organ function by down regulation of pro-inflammatory cytokine release and maintenance of blood level balance with pro-inflammatory cytokines. Mateial and Method: Plasma IL-10 levels were measured and analyzed in 22 patients who underwent open heart surgery (11 cases of coronary artery bypass graft, 11 cases of valve replacement) under cardiopulmonary bypass since 1988 January to July at Department of Thoracic and Czardiovascular surgery, Yeungnam University Hospital. 1g of methylprednisolone was administrated to thirteen patients randomly. Blood samp.es were taken and collected at the time of induction of anesthesia, 10 min before cardiopulmonary bypass, 10 min after starting of CPB, 10 min aftr aortic cross clamping, 10 min after ACC release, and 10 min, 2 hours, and `5 hours after CPB respectively. The plasma levels of IL-10 were determined by enzyme-linked immunosorbent assays(ELISA). Wilcoxon-Raule Sum test was used for statistical analysis. Result: In all 22 patients, cardiopulmonary bypass time was used for statistical analysis. Result: In all 22 patients, cardiopulmonary bypass time was 171$\pm$41.4 min and aortic cross clamp time was 118$\pm$36.5 min. Peak IL-10 level was achieved at 10 min after ACC(361.0$\pm$52.81pg/ml) and was decreased sharply at 2 hours after CPB. Peak IL-10 level was correlated positively with aortic cross clamp time(p=0.011); however, it did not correlated with bypass time(p=0.181). In valve replacement group, mean IL-10 level at peak point was 567.89$\pm$107.69 pg/ml and was significantly higher than that of coronary artery bypass group(205.67$\pm$192.70 pg/ml)(p<0.001). ACC time in valve replacement group was significantly longer than that of coronary artery bypass group(p<0.01), however, bypass time was not(p=0.212). Thirteen patients with steroid pretreatment before starting of CPB showed relatively higher plasma IL-10 level than in control group, however, no statistical significance was noted(p=0.19). Conclusion: plasma level of IL-10 was increased in association with cardiopulmonary bypass and revealed peak at 10 min after ACC release. IL-10 level was correlated positively with ACC time. Therefore, systemic inflammatory respeonse in association with cardiopulmonary bypass could be decreased by reducing ACC time during cardiac surgery.

• 대한한방소아과학회지
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• 제19권1호
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• pp.185-201
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• 2005

Objective : This experimental study was performed to examine the anti-allergic infiammatory effects of Mori Folium. Method : Macrophage 264.7 cells were pretreated for 1hour with Sangyup. After pretreatment, macrophage were incubated with lipopolysaccharide(LPS) $100ng/m{\ell}$ 12h and media collected and $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, IL-10 concentrations in supernatants were measured each by Enzyme linked immuno-sorbent assay. Sangyup were used $1mg/m{\ell}$, $500{\mu}g/m{\ell}$, $250{\mu}g/m{\ell}$, $100{\mu}g/m{\ell}$, $50{\mu}g/m{\ell}$. Hydrocortisones were used $10^{-4}M,\;10^{-5}M,\;10^{-6}M,\;10^{-6}M,\;10^{-6}M$. Results : Macrophage 264.7 cells were pretreated with Hydrocortisones and Sangyup. After pretreatment, macrophage were incubated with lipopolysaccharide(LPS). To investigate the anti-inflammatory effect of Sangyup, we measured the amount of cytokines, and the results are as follows; 1. Mori Folium. showed statistically significant inhibitory effect on antiinflammation in $TNF-{\alpha}(p<0.02)$ in all five concentrations compared with the (-)controls treated with LPS. Mori Folium showed inhibitory effect on antiinflammation in $TNF-{\alpha}$ in similarpattern in all five concentrations compared with the (+)control pretreated with hydrocortisone. 2. Mori Folium. showed statistically significant inhibitory effect on antiinflammation in IL-6(p<0.01) in all five concentrations compared the (-)controls treated with LPS. Mori Folium. showed inhibitory effect on antiinflammation IL-6 similar pattern in all five concentrations compared with the (+)control pretreated with hydrocortisone. 3. Experimental Group pretreated with Mori Folium. showed statistically significant difference of antiinflammation in $IL-1{\beta}$ in concentrations of $50{\mu}g/m{\ell}(p<0.01)$, $250{\mu}g/m{\ell}(p<0.05)$ compared with the (-)control treated with LPS. Experimental Group pretreated with Mori Folium. showed increased level of $IL-1{\beta}$ in all concentrations compared the (+)control treated with hydrocortisone. 4. Experimental Group pretreated with Mori Folium. did not show statistically significant effect on IL-10 compared with the (-)control. Conclusion : By the findings of this experiment, Mori Folium is observed to have antiallergic and antiinflammation effect.

• Journal of Ginseng Research
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• 제28권2호
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• pp.104-110
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• 2004

본 연구는 근치적 위절제 및 림프절 절제와 혹은 절제불가능 환자에서 항암화학요법 치료를 받는 위암환자에서 홍삼액기스 투여군에서 비록 각군의 대상 개체의 표본수가 적음에도 불구하고 홍삼엑기스 투여군에서 항암 cytokine으로 알려진 IL-2가 위암 대조군에 비하여 높게 나타나고 숙주의 항암 면역기능을 저해하는 cytokine인 IL-10은 수술 후 1개월에 홍삼엑기스 투여군에서 위암 대조군에 보다 그 감소비가 높게 나타났으며, 수술 후 3개월에는 홍삼엑기스 투여군에서만 건강 대조군 값에 접근하는 결과를 보여 보조 항암 화학요법 기간에서 홍삼엑기스의 투여는 위암 환자에서의 숙주의 항암 면역 억제의 현상을 빠른 시간 내에 회복시킬 수 있는 효과가 있는 것으로 보여진다. 대단위 개체를 포함하는 지속적인 추가 연구의 필요성이 절실하며 이러한 추가 연구가 진행 된다면 홍삼엑기스의 위암환자에서의 항암 면역기능의 역할을 임상적으로 증명 할 수 있으리라고 기대 된다.

• 대한본초학회지
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• 제32권3호
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• pp.1-7
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• 2017

Objective : The purpose of this study was to investigate the effects of Scrophulariae Radix Water Extract (SR) on the production of inflammatory mediators in RAW 264.7 mouse macrophages cells induced by lipopolysaccharide (LPS). Method : We examined effect of Scrophulariae Radix Extract on the cell viability of mouse macrophages cells. Futhermore, After 24 hours treatment we investigated anti-inflammatory effect of Scrophulariae Radix Extract by the production of Bio-Plex cytokine assay, concentrations of various cytokines such NO, $interleukin(IL)-1{\alpha}$, IL-3 and interferon inducible protein-10(IP-10). Result : No significant changes have been found in the mouse macrophge cell viability by the Scrophulariae Radix Extract at the concentration of 25, 50, 100 and $200{\mu}g/m{\ell}$. The water extract of Scrophulariae Radix significantly inhibited the production of NO in the LPS-induced macrophage at the concentration of 25, 50, 100 and $200{\mu}g/m{\ell}$. The water extract of Scrophulariae Radix significantly inhibited the production of $IL-1{\alpha}$, IL-3 and IP-10 in the LPS-induced macrophage at the concentration of 50, 100 and $200{\mu}g/m{\ell}$. Conclusion : The water extract of Scrophulariae Radix significantly inhibited the production of NO, $IL-1{\alpha}$, IL-3 and IP-10 at the concentration of $50{\mu}g/m{\ell}$ or higher in the LPS-induced macrophages with no changes in the cell viability of them. These results suggest that water extract of Scrophulariae Radix has anti-inflammatory effect related with its inhibition of proinflammatory cytokines such as $IL-1{\alpha}$, IL-3 and IP-10 in the LPS-induced macrophages.

• Bulletin of the Korean Chemical Society
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• 제22권10호
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• pp.1159-1162
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• 2001

• BMB Reports
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• 제49권5호
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• pp.293-296
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• 2016

The immunoregulatory cytokine Interleukin 10 (IL-10) protein is produced by various cells during the course of inflammatory disorders. Mainly, it downregulates pro-inflammatory cytokines, antigen presentation, and helper T cell activation. In this study, we show that the ratio of IL-10-producing cells was significantly increased in lineage negative (i.e., not T, B, or leukocyte cell lineages) cells than in lineage positive cells in lymphoid and peripheral tissues. We further observed that IL-10-producing innate lymphoid cells (ILCs), here called firstly ILC10, were increased in number in oxazolone-induced contact hypersensitivity (CHS) mice. In detail, IL-10-producing lineage negative cells were elevated in the axillary, inguinal lymph node, and ear tissues of CHS mice. Notably, the cells expressed classical ILC marker proteins such as CD45, CD127, and Sca-1. Altogether, our findings suggest for the first time that ILC10s are present in various physiological settings and could be involved in numerous immune responses as regulatory cells.

• 한방재활의학과학회지
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• 제20권3호
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• pp.27-35
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• 2010

Objectives : The present study investigated anti-inflammatory effect of Artemisia Capilaris Thunberg in lipopolysaccharide-exposed rats. Methods : We divided lipopolysaccharide-exposed Sprague-Dawley rats into 4 groups. They were normal group, feed with 100 mg/kg Artemisia Capillaris Thunberg group, feed with 200 mg/kg Artemisia Capillaris Thunberg group and feed with 300 mg/kg Artemisia capilaris Thunberg group. They were administered for 6 weeks. We measured counts of red blood cell(RBC), the values of hemoglobin(Hb) and packed cell volume(PCV), plasma total protein concentration, albumin concentration, the ratio of albumin/globulin, the activities of plasma glutamic oxaloacetic transaminase(GOT), glutamic pyruvic transaminase(GPT), lactate dehydrogenase(LDH), the counts of white blood cell(WBC), the ratio of neutrophils, lymphocytes, monocytes, basophils, eosinophils, the concentration of plasma interleukin-$1{\beta}$($IL-1{\beta}$), plasma interleukin-6(IL-6), plasma tumor necrosis factor-$\alpha$($TNF-{\alpha}$), plasma interleukin-10(IL-10), the concentration of liver $IL-1{\beta}$ and IL-6, $TNF-{\alpha}$, IL-10. Results : Counts of RBC and the values of Hb and PCV, plasma total protein concentration and albumin concentration, the activities of plasma GOT, GPT and LDH showed no significant difference in the treatment groups. and the ratio of albumin/globulin was increased in Artemisia Capillaris Thunberg groups. The counts of WBC showed lower values in Artemisia Capillaris Thunberg groups than those of control group, In the ratio of neutrophils Thunberg groups. The ration of monocytes, basophils and eosinophils were below 5%, and showed no characteristic trend. The concentration of plasma interleukin-$1{\beta}$($IL-1{\beta}$), plasma inerleukin-6(IL-6) and plasma tumor necrosis factor-$\alpha$($TNF-{\alpha}$) showed a lower values in the Artemisia Capillaris Thunberg groups than those of control group, and the concentration of plasma interleukin-10(IL-10) showed no significant difference in the treatment groups. The concentration of liver $IL-1{\beta}$ and IL-6 showed a lower values in the Artemisia Capillaris Thunberg groups than those of control group, however the concentration of liver $TNF-{\alpha}$ and IL-10 showed no significant difference in the treatment groups. Conclusions : The Artemisia Capillaris Thunberg groups gives positive results of anti-inflammatory response by lipopolysaccharide(LPS) derivation.

• BMB Reports
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• 제40권1호
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• pp.36-43
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• 2007

In this study, cutaneous role of IL-4 in UVB-induced apoptosis was investigated using transgenic mice with skin-specific expression of IL-4 (IL-4 Tg mice). The transgenic mice did not show any gross clinical abnormalities. However, epidermis was thickened and increased MHC class II positive cells were detected as well as enhanced expression of inflammatory cytokines such as IL-1 and TNF-$\alpha$ in skin. In addition, histological analysis revealed increased infiltration of lymphocytes, acanthosis, hyperkeratosis, and parakeratosis in skin of IL-4 Tg mice. The physiological effect of IL-4 overexpression in skin against environmental stimulus such as UVB was investigated by irradiating wild-type and IL-4 Tg mice with UVB followed by evaluation of apoptosis. The result demonstrated suppressed apoptosis in epidermis of IL-4 Tg mice compared with wild-type mice. To further assess anti-apoptotic function of IL-4 in keratinocytes, stable cell clones were made where IL-4 was constitutively overexpressed and examined for UVB-induced apoptosis. The results showed that apoptosis was remarkably decreased in IL-4 over-expressing cell clones compared with that in mock transfected cells. Collectively, data presented here shows that IL-4 has an inhibitory effect against UVB-induced apoptosis in keratinocytes, suggesting that IL-4 may be an important regulator in cutaneous immunity against UVB.

• 동의생리병리학회지
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• 제23권2호
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• pp.452-456
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• 2009

The purpose of this study was to investigate the anti-inflammatory effects and cellular mechanism of piperine on murine peritoneal macrophages. To evaluate the effects of piperine, we examined the production of nitric oxide (NO), interleukin (IL)-10 and IL-12. To investigate inhibitory mechanism of piperine, we examined the MAPKs and Ik-Ba in murine peritoneal macrophages, Piperine itself does not have any cytotoxic effect and reduced lipopolysaccharid (LPS), Poly(I:C), CpG-ODN -induced production of NO, IL-10 and IL-12 in peritoneal macrophages. Piperine inhibited the activation of extracelluar signal-regulated kinase (ERK 1/2) and c-Jun NH2-terminal kinase (JNK 1/2) not the activation of p38 and the degradation of inhibitory kappa B a (Ik-Ba) in the LPS-stimulated murine peritoneal macrophages.ln conclusion, Piperine down-regulated LPS-induced production of NO, IL-10 and IL-12, which could provide a clinical basis for anti-inflammatory properties of piperine.