• Archives of Pharmacal Research
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• 제26권5호
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• pp.383-388
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• 2003

Bee venom is used as a traditional medicine for treatment of arthritis. The anti-inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions from bee venom (Apis mellifera) was studied using cyclooxygenase (COX) activity and pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production, in vitro. COX-2 is involved in the production of prostaglandins that mediate pain and support the inflammatory process. The aqueous partition of bee venom showed strong dose-dependent inhibitory effects on COX-2 activity ($IC_{50} = 13.1 \mu$ g/mL), but did not inhibit COX-1 activity. The aqueous partition was subfractionated into three parts by molecular weight differences, namely, B-F1 (above 20 KDa), B-F2 (between 10 KDa and 20 KDa) and BF-3 (below 10 KDa). B-F2 and B-F3 strongly inhibited COX-2 activity and COX-2 mRNA expression in a dose-dependent manner, without revealing cytotoxic effects. TNF-$\alpha and IL-1\beta$ are potent pro-inflammatory cytokines and are early indicators of the inflammatory process. We also investigated the effects of three subfractions on TNF-$\alpha and IL-1\beta$ production using ELISA method. All three subfractions, B-F1, B-F2 and B-F3, inhibited TNF-$\alpha and IL-1\beta$production. These results suggest the pharmacological activities of bee venom on anti-inflammatory process include the inhibition of COX-2 expression and the blocking of pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production.

• 대한한방내과학회지
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• 제27권4호
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• pp.864-878
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• 2006

목적 : 인삼은 다양한 생물학적 작용이 있다. 그 중 항염증작용과 관련하여 염증성 사이토카인 분비 및 저산소 유도인자-1${\alpha}$ 활성화 조절 효과를 살펴보고자 한다. 방법 : phorbol myristate acetate (PMA)+A23187에 유도된 세포에서 염증성 cytokines 분비의 변화와 인간의 mast cell인 HMC-1 cells에서 hypoxia-inducible factor-1 (HIF-1)${\alpha}$의 작용을 관찰하였다. 결과 : PMA+A23187은 대조군과 비교해서 interleukin $(IL)-1{\beta}$, IL-6와 tumor necrosis factor $(TNF)-{\alpha}$의 분비를 증가시킨다. 또한 증가된 cytokines IL-1, IL-6, $TNF-{\alpha}$가 인삼의 처리에 의해 두드러지게 억제하는 것을 확인하였다. 인삼(5 ${\mu}g/ml$)은 $IL-1{\beta}$, IL-6, $TNF-{\alpha}$의 분비를 약 105.1${\pm}$9.7%, 95${\pm}$9.4%, 29.7${\pm}$4.5%,(P<0.05)로 최대로 억제하였고, PMA+A23187에 유도된 vascular endothelial growth factor (VEGF)와 granulocyte macrophage-colony stimulating factor (GM-CSF)의 분비를 41.3%와 75.7%로 각각 억제하였다. 그리고 저자는 인삼이 PMA+A23187로 유도된 HIF-1${\alpha}$ 발현과 HIF-1에 대해 DNA binding activity를 억제하고 있음을 관찰하였다. 결론 : 인삼이 HIF-1에서 염증반응을 억제함을 나타내고, 이는 인삼이 염증성 질환을 치료하는데 유익한 효과가 있음을 의미한다.

• 한방재활의학과학회지
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• 제23권2호
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• pp.73-83
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• 2013

Objectives : This study was performed to investigate the effects of Foeniculum Vulgare(FV) extract on the anti-inflammatory of lipopolysaccharide(LPS) exposed rats. Methods : We divided LPS exposed Sprague-Dawley rats into 4 groups. They were control group, feed with 100 mg/kg, 200 mg/kg, 300 mg/kg FV groups. They were administered for 6 weeks. We measured 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${\beta}$, IL-6, TNF-${\alpha}$ and IL-10. Results : 1. Plasma IL-1${\beta}$, plasma IL-6 and plasma TNF-${\alpha}$ concentration increased rapidly at 2hours after LPS injection and maintained high levels at 5hours after LPS injection. The concentration of these cytokines in the FV extract groups showed lower values than control group(P<0.05). 2. The concentration of Plasma IL-10 in FV extract groups showed higher values than control group at all times(P<0.05). 3. The concentration of liver IL-1${\beta}$ and IL-6 in FV extract groups showed lower values than control group(P<0.05). The concentration of liver TNF-${\alpha}$ in FV extract groups showed a tendency to decrease and that of liver IL-10 in FV extract groups showed a tendency to increase; however, these values showed no significantly different. Conclusions : In inflammatory response by LPS derivation, the FV gives positive effect.

• 한국식품영양학회지
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• 제21권1호
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• pp.1-6
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• 2008

Job's Tears(Yul-Moo) is a grass crop long-used as a traditional medicine; it is also a nourishing food. There are reports of its anti-inflammatory, stomachic, antiallergic activity, and antispastic effects and Job's Tears has been used in China to treat rheumatism, and neuralgia although its warts, rheumanism remains unclear. Thus, the present study was performed to investigate the in vitro effect of Job's Tears extracts on immune function. Here mouse splenocyte proliferation and cytokine production$(IL-1{\beta},\;IL-6,\;TNF-{\alpha})$ by peritoneal macrophages cultured with ethanol and water extracts of Job's Tears were examined. splenocytes proliferation increased with Job's Tears water extracts supplement at concentrations investigated The cytokine production$(IL-1{\beta},\;IL-6,\;TNF-{\alpha})$ by ELISA using a cytokine kit And $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production increased water extracts supplementation. This in vitro study suggests that supplementation with Job's Tears water extracts may enhance immune function by regulating the splenocyte proliferation and enhancing cytokine production of activated macrophages.

• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.185-189
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• 2010

The present study demonstrates the effect of fibrates, agonists of $PPAR{\alpha}$ on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-$1{\beta}$ (10 ng/ml), $IFNP{\gamma}$ (10 ng/ml), and TNF-$\alpha$ (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and $10\;{\mu}M$) reduced the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation, released IL-6 level was measured. $IFNP{\gamma}$ and IL-$1{\beta}$ cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in $IFNP{\gamma}$ and IL-$1{\beta}$-stimulated astrocytes. Taken together, these results clearly suggest that activation of $PPAR{\alpha}$ attenuates the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation through IL-6 independent pathway.

• Safety and Health at Work
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• 제1권1호
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• pp.69-79
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• 2010

Objectives: Various cytokines induced by inhalation of coal dust may mediate inflammation and lead to tissue damage or fibrosis, such as coal workers' pneumoconiosis (CWP). Methods: To investigate the relevance of serum cytokines in CWP, the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-${\alpha}$) as CWP biomarkers in 110 retired coal miners (22 controls and 88 CWP subjects) were related to cross sectional findings and 1-year progressive changes of the pneumoconiosis. Progressive changes of CWP were evaluated by paired comparison of chest radiographs. Analysis by a receiver operating characteristic curve assessed the biomarker potential of each cytokine. Results: The mean serum IL-8 level was significantly higher in CWP compared to controls and IL-8 levels correlated with the degree of CWP. The median serum TNF-${\alpha}$ level was significantly higher in subjects with progressive CWP compared to subjects without CWP progression. The area under the ROC curve for IL-8 (0.70) and TNF-${\alpha}$ (0.72) for CWP identification and progression, respectively, indicated the biomarker potential of the two cytokines. Serum cutoff values of IL-8 and TNF-${\alpha}$ were 11.63 pg/mL(sensitivity, 69%; specificity, 64%) and 4.52 pg/mL (sensitivity, 67%; specificity, 79%), respectively. Conclusion: The results suggest that high levels of serum IL-8 are associated with the presence of CWP and those of serum TNF-${\alpha}$ are associated with the progression of CWP.

• 대한한의학방제학회지
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• 제21권2호
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• pp.81-89
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• 2013

Objectives : The purpose of this study is to observe the effect of Coptidis Rhizoma (CCE-extract of C. chinensis Rhizome) in induction of immune protein on mouse macrophages. Methods : To analyze cytokines interleukin(IL)-$1{\alpha}$, IL-3, IL-9, IL-12p40, IL-13, IL-17, Monocyte Chemoattractant Protein(MCP)-1 induced by macrophages, mouse macrophages were incubated with CCE and was measured. Results : IL-$1{\alpha}$ measurement, CCE showed significant inhibition only at concentration level of 200 ${\mu}g/mL$. IL-3, MCP-1 measurement, CCE showed significant inhibition only at concentration level of 100, 200 ${\mu}g/mL$. IL-9 measurement, CCE showed significant inhibition only at concentration level of 50 ${\mu}g/mL$. IL-13 measurement, CCE showed significant inhibition only at concentration level of 50, 100, 200 ${\mu}g/mL$. The IL-12p40, IL-17 levels indicated no changes at 25, 50, 100, 200 ${\mu}g/mL$ on mouse macrophages. Conclusions : CCE did not significantly increased inflammatory cytokines IL-$1{\alpha}$, IL-3, IL-9, IL-12p40, IL-13, IL-17, Monocyte Chemoattractant Protein(MCP)-1 on mouse macrophages. It was verified CCE does not trigger cytokine related hypersensitivity reaction of organism or exacerbation of acute/chronic inflammatory disease.

• 동의신경정신과학회지
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• 제11권2호
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• pp.11-21
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• 2000

Substance P(SP) can stimulate production of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) from astrocytes stimulated with lipopolysaccharide(LPS). The objective of the current study was to determine the effect of Taraxacum officinale(TO) on the production of TNF-${\alpha}$ from primary cultures of rat astrocytes. TO(100& 1000$\mu\textrm{g}$/ml) significantly inhibited the TNF-${\alpha}$ production by astrocytes stimulated with LPS and SP. Interleukin-1(IL-1) has been shown to elevate TNF-${\alpha}$ production from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-${\alpha}$ production from primary astrocytes by TO. Treatment of TO(100 and 1000$\mu\textrm{g}$/ml) to astrocytes stimulated with both LPS and substance P decreased IL-1 production significantly. Moreover, the production of TNF-${\alpha}$ by LPS and substance P in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. These results suggest that TO may inhibit TNF-${\alpha}$ production by inhibiting IL-1 production and that TO has an antiinflammatory activity in the central nervous system.

• 대한한방내과학회지
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• 제27권1호
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• pp.228-236
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• 2006

Objectives : Macrophage has an important innate defense role in the immune system. When we are infected with pathogens, macrophage ingests them through phagocytosis or endocytosis, and then secretes many cytokines, such as IL-1, IL-6 and $TGF{\alpha}$, which are regulators of immune responses. The aim of this study is to determine how Samjunghwan effects the expression of cytokine and other immune-related genes in macrophages. Methods : Cells were treated directly with Samjunghwan and/or LPS at regular intervals. Total RNA of cells was isolated using TRIzol reagent, and the changes in cytokine gene expressions were investigated using RT-PCR, western blot and ELISA. Results : $IL-1{\alpha},\;IL-1{\beta}$ and COX-2 genes were inducibly expressed specifically by Samjunghwan in macrophage. Especially, $IL-1{\beta}$ gene was induced most strongly by treatment with Samjunghwan. Over time, treatment with Samjunghwan showed that the expression levels of $IL-1{\alpha}\;and\;$IL-1{\beta}$ genes increased from 1 to 4h, and then decreased from 4 to ISh. However, the expression level of COX-2 gene increased continuously up to 11h. $IL-1{\alpha},\;IL-1{\beta}$ and COX-2 genes were expressed synergistically by a simultaneous treatment of both Samjunghwan and LPS in macrophages. Secretion levels of translated $IL-1{\beta}$ increased continuously up to 11h. Conclusions : Though this study is only a start in the investigation of the efficasy of Samjunghwan, these results suggest that Samjunghwan has positive effects on immune responses.

• Tuberculosis and Respiratory Diseases
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• 제55권2호
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• pp.140-153
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• 2003

연구배경 : 결핵균 항원으로 세포 매개성 면역반응이 활성화되면 여러 종류의 cytokine이 분비되고 각기 다른 cytokine과 network system으로 작용하여 여러 병태생리적인 과정을 조절한다. 결핵 환자에서 염증반응, 조직파괴 및 질환의 중증도는 proinflammatory cytokine과 suppressive cytokine의 균형과 조합에 의하여 결정되며, 결핵 진행의 제한과 악화에 중요한 역할을 할 것으로 생각되고 있다. 따라서 결핵의 이환과정에서 cytokine의 분비 및 변화와 역할을 파악하는 것이 질환의 병태생리를 이해하는데 크게 도움이 될 수 있다. 대상 및 방법 : 활동성 폐결핵 83명, 기관지 결핵 10명의 치료전과 정상 대조군 20명에서 말초혈액을 채취하여 혈청을 분리하여 $-70^{\circ}C$에 보관하였고, sandwich ELISA 방법을 이용하여 혈청 IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$, TGF-${\beta}$를 측정하였다. 폐결핵 환자 83명을 ATS guideline에 따라 중증도를 분류하였고, 추적관찰 중 탈락자를 제외한 45명에서 초치료 2개월과 6개월 후 각각 혈청 sIL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$, TGF-${\beta}$를 재측정하였다. 결 과 : 1) IL-$1{\beta}$, TNF-${\alpha}$, IFN-${\gamma}$는 폐결핵 환자에서 대조군에 비하여 증가된 경향을 보였고(p>0.05), IL-6는 폐결핵군에서 통계적으로 유의하게 증가되었다(p<0.05). TGF-${\beta}$는 폐결핵과 기관지 결핵환자에서의 분비가 대조군에 비하여 감소된 경향을 보였으며(p>0.05), IL-2, IL-12(p40), IL-4, IL-10은 대조군과 폐결핵 환자에서 별다른 차이를 보이지 않았다. 2) 기관지 결핵 환자에서 IL-6, TNF-${\alpha}$는 대조군에 비해 증가되고 TGF-${\beta}$는 감소된 경향을 보였다(p>0.05). 폐결핵에 비해 IL-12(p40)의 분비는 증가된 경향을 보였다. 3) 결핵의 중증도가 심할수록 IFN-${\gamma}$와 IL-6가 유의하게 증가하였고(P<0.05), 특히 중증군에서 현저하였다. 4) 폐결핵 환자에서 치료전 측정한 IL-$1{\beta}$, IL-6, TNF-${\alpha}$ 간 및 IL-2, IL-4, IL-12 간에는 강한 양의 상관관계를 보였다(p<0.01). 5) 폐결핵 환자 45명에서 측정한 IL-6와 IFN-${\gamma}$는 치료후 2개월과 6개월에 각각 통계적으로 유의하게 감소되었다(p<0.05). 결 론 : 이상의 결과로 결핵의 병태생리에 있어서 여러 cytokine간의 균형과 조합의 변화가 숙주의 염증, 조직파괴 및 결핵의 중증도와 관련되어 있을 것으로 생각되지만 결핵의 형태나 면역반응 정도에 따른 다양성을 보여서 결과의 해석과 cytokine 측정의 임상적 이용에 대한 연구가 더욱 필요할 것으로 사료된다.