• Title/Summary/Keyword: IFN-gamma

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Chemoprevention of Helicobacter pylori-associated Gastric Carcinogenesis in a Mouse Model; Is It Possible?

  • Hahm, Ki-Baik;Song, Young-Joon;Oh, Tae-Young;Lee, Jeong-Sang;Surh, Young-Joon;Kim, Young-Bae;Yoo, Byung-Moo;Kim, Jin-Hong;Ha, Sang-Uk;Nahm, Ki-Taik;Kim, Myung-Wook;Kim, Dae-Yong;Cho, Sung-Won
    • BMB Reports
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    • v.36 no.1
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    • pp.82-94
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    • 2003
  • Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-${\kappa}B$ binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-${\kappa}B$ binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-$\gamma$, RANTES, TNF-$\alpha$, TNFR p75, IL-$1{\beta}$ in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric/cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.

Anti-Allergic Activities of Fermented Eriobotrya japonica and Saurus chinensis Extracts in 2,4-Dinitrochlorobezene-Induced BALB/c Mice (2,4-Dinitrochlorobenzene으로 유도된 아토피 피부염 동물모델에서 비파엽 및 삼백초 추출발효물의 항아토피 활성)

  • Choi, Myung-Jin;Jung, Hee-Kyoung;Jeong, Yoo-Seok;Park, Seung-Chun;Hong, Joo-Heon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.11
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    • pp.1611-1618
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    • 2010
  • This study was conducted to evaluate the effects of Eriobotrya japonica and Saurus chinensis extracts and their fermented extracts on immune parameters in BALB/c mice treated with 1% 2,4-dinitrochlorobenzene (DNCB). The groups were Eriobotrya japonica extract (BI), Saurus chinensis extract (SA), mixture with E. japonica extract and S. chinensis extract (FB) and fermented mixture with E. japonica extract and S. chinensis extract (FA) and distilled water treated control. The level of serum immunoglobulin (Ig) E was decreased in FA compared to control group, but significant difference was not observed (p<0.05). The histamine and contents in FA and control group were $1.47{\pm}0.20$ ng/mL and $1.90{\pm}0.04$ ng/mL, respectively (p<0.05). Ceramide contents were significantly increased in FA compared to BI, SA, FB and control group (p<0.05). These results suggest that FA supplementation in the DNCB treated BALB/c mice affect anti-allergic activities positively, and may be used as functional material for suppression of atopy dermatitis in food industry.

$NO_2^-$ and ATP synthesis in the EMT-6 cell stimulated by mercury chloride (수은에 의한 EMT-6 세포의 $NO_2^-$ 및 ATP 생성)

  • Oh, Gyung-Jae;Koh, Dai-Ha;Youm, Jung-Ho
    • Journal of Preventive Medicine and Public Health
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    • v.29 no.3 s.54
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    • pp.495-505
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    • 1996
  • Effect or mercury chloride on the synthesis or $NO_2^-$ and ATP were observed in EMT-6 cells which were cultured with cytokines$(IL-1\alpha\;and\;IFN-\gamma)$ and various concentrations of mercury chloride from 0.05 to $0.8{\mu}M$. Viability of EMT-6 cells were observed above 90% in almost groups. There were not significant differences in the viability between mercury supplemented groups and control group. It suggests viability of EMT-6 cells were not influenced by these concentrations of mercury chloride. Results of the synthesis of nitrite showed significant time and group effect. There is a significant interaction effect between concentration of mercury chloride and culture time. The effect of various concentration of mercury chloride is not the same for all levels of culture time. There were significant differences in the synthesis of nitrite between mercury chloride supplemented groups and control group, and the synthesis of nitrite in EMT-6 cell by the supplement of mercury chloride was significantly decreased in a dose-dependent manner. Results of the synthesis of ATP showed a significant group effect, and the time main effect and the $Group{\times}Time$ interaction were also significant. There were significant differences in the synthesis of ATP between mercury chloride supplemented groups and control group, and the synthesis of ATP in EMT-6 cell by the supplement of mercury chloride was significantly decreased in a dose - dependent manner. These results suggest that the disorder of cell mediated immunity by mercury chloride could be related to the inhibition of nitric oxide synthesis which will be caused by the decreased synthesis of ATP.

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Production of Nitric Oxide in Raw 264.7 Macrophages treated with Ganoderan, the ${\beta}-Glucan$ of Ganoderma lucidum (영지의 균사체성 ${\beta}-glucan$에 의한 Raw 264.7 대식세포의 Nitric Oxide생성)

  • Han, Man-Deuk;Lee, Eun-Sook;Kim, Young-Kweon;Lee, June-Woo;Jeong, Hoon;Yoon, Kyung-Ha
    • The Korean Journal of Mycology
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    • v.26 no.2 s.85
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    • pp.246-255
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    • 1998
  • Ganoderan (GAN), an immunomodulating ${\beta}-glucan$ of G. lucidum, induces potent antitumor immunity in tumor-bearing mice. This study was set up to elucidate the ability of macrophage activation of GANs. GAN-treated Raw 264.7 macrophages showed enhanced production of nitric oxide (NO). The ability of GANs to produce NO was based on differences in chemical composition of GANs obtained from the mycelium on various carbon sources and mycelial fractionation. The highest NO production was observed in CW-AS-WS polysaccharide which was extracted from the mycelial wall. GAN-treated Raw 264.7 cells gave a 2-to 5-fold (24 hr) formation of NO levels compared with those treated with medium only. Partial removal of the protein in the extracellular GAN by TCA treatment did appreciably reduce its capacity to secrete NO. The mixture effect of GAN and LPS increased the nitric oxide secretion from RAW 264.7. The cell proliferation of GAN-treated Raw 264.7 cell tines inhibited as compared with its control. Of the culture supernatant of macrophage activated by GAN, the percentage of cytotoxicity against mouse leukemia L1210 cells was slightly dependent on the amount of NO in the culture supernatants of the activated-macrophages. These results indicate that the ${\beta}-glucan-related$ polysaccharides of the higher fungus activate macrophage and release nitric oxide. It also suggests that murine macrophages possess certain receptors for ${\beta}-anomeric$ glucans and play a critical role of ${\beta}-glucan-related$ tumor killing mechanism.

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The Role of Lymphocyte Compartment and Cytokine in Coal Workers Pneumoconiosis (진폐증환자에서의 임파구 분획 및 싸이토카인의 역할)

  • Lee, Jung-Yeon;Yoo, Kwang-Ha;Ahn, Hae-Ryon;Kim, Sung-Ryul;Lee, Hae-Woon;Ahn, Cheol-Min;Kim, Hyung-Joong
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.3
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    • pp.241-250
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    • 2002
  • Background : Coal-worker's pneumoconiosis(CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in the alveolar spaces. CWP is usually divided into two stage : simple pneumoconiosis(SP) where there are a limited number of fibrotic lesions remain limited, with radiological opacities smaller than 1cm and progressive massive fibrosis(PMF), which is characterized by the development of a perifocal extensive fibrotic response of the lung and severe alterations in pulmonary function. In this study, the lymphocyte compartment and cytokine were evaluated by measuring the serum levels in the control, SP and PMF groups. Materials and Methods : The coal workers selected for this study were employees(patients?) of the Tae-Baek and Dong-Hae hospital. All were men, 45-76 years old and the mean duration of their exposure to coal dust was 23.2 years in the lymphocyte compartment and 24.3 years in the cytokine checked group. According to X-ray examination results, the patients were classified into either one of the SP, PMF categories. The normal controls examined were 26-70 years old men. The serum cytokine levels were estimated by using an end point enzyme immunoassay technique. Results : T lymphocyte, helper and suppressor T cells were highly related to pneumoconiosis in this study. A statistically significant decrease in the number of suppressor T lymphocytes was observed in the simple pneumoconiosis patients and at the same time, there was an increase in the lymphocyte index. Howevere, there was no statistically difference in the serum cytokines levels among the SP, PMF and control groups. Conclusion : T lymphocyte, helper T, and suppressor T cells may be highly related to the development of CWP compared to the control group particularly in the early stage of pneumoconiosis. The changes observed in the immunological system in patients with pneumoconiosis may lie at the bottom of the pathogenesis of fibrosis. Further study is needed to evaluate the lymphocyte compartment as a marker for pneumoconiosis development in the early stage.

Antioxidant and Immunological Activities of Polysaccharide Extracted from Cultured Mycelia of Schizophyllum commune (치마버섯 균사체 배양물로부터 분리한 다당류의 항산화 및 면역 활성)

  • Lee, June-Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.9
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    • pp.1334-1341
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    • 2014
  • To examine the biological activity of polysaccharide extracted from cultured mycelia of Schizophyllum commune, we determined anti-complementary activity and nitric oxide production as a measure of immunological activity, anti-lipidperoxidation and hydroxy radical scavenging activity as a measure of antioxidative activity, tyrosinase inhibitory activity, anti-microbial activity, and transdermal flux of polysaccharide extracted from cultured mycelia of S. commune. Polysaccharide extracted from S. commune activated the complementary system and produced nitric oxide in RAW 264.7 macrophages. Antioxidant activities as malondialdehyde values were $49.5{\pm}0.7$, $39.7{\pm}1.7$, $39.2{\pm}1.2$, and $2.6{\pm}0.5nM/mL$ for control, extracellular polysaccharide extracted from S. commune (SC-EP), ultrafiltrated polysaccharide extracted from S. commune (SC-UP), and butylated hydroxytoluene, respectively. Hydroxy radical scavenging activity ($IC_{50}$) of SC-UP and mannitol were 3.32 and 1.66 mg/mL, respectively. Tyrosinase inhibitory activities of SC-UP, arbutin, and kojic acid were 19.9%, 31.8%, and 99.0%, respectively. Anti-microbial activities of SC-UP appeared to be low, and transdermal fluxes of SC-UP were 0.47%, 0.73%, and 1.20% after 3, 6, and 9 hr, respectively. These findings suggest that polysaccharide extracted from S. commune has potential immunological and antioxidant activities.

GATA-3 is a Key Factor for Th1/Th2 Balance Regulation by Myristicin in a Murine Model of Asthma (Myristicin이 Ovalbumin으로 유도한 천식 생쥐모델에서 Th1/Th2 Balance를 조절하는 GATA-3에 미치는 효과)

  • Lee, Kyu;Lee, Chang-Min;Jung, In-Duk;Jeong, Young-Il;Chun, Sung-Hak;Park, Hee-Ju;Choi, Il-Whan;Ahn, Soon-Cheol;Shin, Yong-Kyoo;Lee, Sang-Yull;Yeom, Seok-Ran;Kim, Jong-Suk;Park, Yeong-Min
    • Journal of Life Science
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    • v.17 no.8 s.88
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    • pp.1090-1099
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    • 2007
  • Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

The Effects of Bee Venom and Melittin Solution on PGE2, COX-2, and NF-kB Dependent Luciferase Activity in RAW 264.7 Cells (봉약침액(蜂藥鍼液)과 Melittin 약침액(藥鍼液)이 RAW 264.7 세포의 PGE2, COX-2 및 NF-kB에 미치는 영향(影響))

  • Jeong, Il-kook;Song, Ho-sueb
    • Journal of Acupuncture Research
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    • v.21 no.6
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    • pp.19-36
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    • 2004
  • Objective : The purpose of this study was to investigate the effect of Bee Venom and Melittin Solution on the lipopolysaccharide(LPS) and sodium nitroprusside(SNP)-induced expression of prostaglandin $E_2(PGE_2)$, cyclooxygenase-2(COX-2), nuclear factor kappa B($NF-{\kappa}B$) and nuclear factor kappa B($NF-{\kappa}B$) dependent luciferase activity in RAW 264.7 cells, a murine macrophage cell line. Methods : The expression of PGE2 was determined by determination of $PEG_2$, COX-2 was by western blotting with corresponding antibodies, $NF-{\kappa}B$ was by gel mobility shift assay method and $NF-{\kappa}B$ dependent luciferase activity was investigated by luciferase assay in RAW 264.7 cells. Results : 1. LPS and SNP-induced expression of $PEG_2$ was significant after 24hour. 2. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS-induced expression of $PEG_2$ and, the $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly SNP-induced expression of $PEG_2$ compared with control, respectively. The 0.5 and $1{\mu}g/mL$ of bee venom could not significantly inhibit SNP-induced expression of $PEG_2$ compared with control. 3. The $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS and SNP-induced expression of COX-2 compared with control, respectively. The 0.5 and $1{\mu}g/mL$ of bee venom inclined to decrease LPS and SNP-induced expression of COX-2 compared with control. 4. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS and SNP-induced expression of $NF-{\kappa}B$ compared with control, respectively. 5. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS-induced expression of $NF-{\kappa}B$ dependent luciferase activity and the 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly SNP-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control, respectively. The $NF-{\kappa}B$ inhibitor also inhibited significantly LPS and SNP-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control. 6. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS + IFN-${\gamma}$, TNF-${\alpha}$ and LPS + TNF-${\alpha}$-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control, respectively. The $NF-{\kappa}B$ inhibitor also inhibited significantly LPS and SNP-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control. Conclusions : These results suggest the inhibitory action of bee venom and melittin solution on the inflammatory mediators such as $PEG_2$, COX-2 and $NF-{\kappa}B$.

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Immunomodulatory effects of β-1,3/1,6-glucan and lactic acid bacteria in LP-BM5 murine leukemia viruses-induced murine acquired immune deficiency syndrome (면역결핍 모델에서 β-1,3/1,6-glucan과 유산균을 이용한 in vivo 면역 활성 조절 효과)

  • Kim, Min-Soo;Kim, JoongSu;Ryu, Min Jung;Kim, Ki hong;Hwang, Kwontack
    • Food Science and Preservation
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    • v.24 no.8
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    • pp.1158-1167
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    • 2017
  • In this study, ${\beta}$-1,3/1,6-glucan, lactic acid bacteria, and ${\beta}$-1,3/1,6-glucan+lactic acid bacteria were tested for 10 weeks using an immunodeficient animal model infected with LP-BM5 murine AIDS virus On the immune activity. Cytokines production, plasma immunoglobulin concentration, T cell and B cell proliferation were measured. As a result, the T cell proliferative capacity which was weakened by immunization with LP-BM5 murine AIDS virus increased significantly T cell proliferative capacity compared with the red ginseng control group. B cell proliferative capacity was significantly higher than the infected control group. Increased B cell proliferation was reduced. In the cytokine production, IL-2, IL-12 and IL-15 in the Th1-type cytokine increased the secretion of IL-2, IL-12 and IL-15 compared to the infected control. The proliferative capacity of the treated group was higher than that of the mixed treatment group. TNF-${\alpha}$ was significantly decreased compared with the infected control group. The IL-4, IL-6 and IL-10 levels were significantly inhibited in the infected control group and the Th1/Th2 type cytokine expression was regulated by immunohistochemistry. IgE, IgA, and IgG levels were significantly lower in the immunoglobulin secretion assay than in the control. As a result, the immunomodulatory effect of ${\beta}$-1,3/1,6-glucan+lactic acid bacteria was confirmed by mixing with LP-BM5 murine AIDS virus-infected immunodeficient animal model.

Interleukin Levels in the Bronchoalveolar Lavage Fluid of Patients with Pulmonary Sarcoidosis (유육종증환자의 기관지폐포세척액내 Interleukin에 대한 연구)

  • Song, Jeong-Sup;Ahn, Joong-Hyun;Kim, Chi-Hong;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.1047-1057
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    • 1998
  • Background : Sarcoidosis is a systemic granulomatous disorder of unknown origin and characterized by accumulation of T cells and macrophages. Various cytokines may play crucial roles in the activation of T cells and macrophages, and thereby in the formation of granulomas. However, little is known about the balance between proinflammatory cytokines and antiinflammatory cytokines in the development of sarcoid granulomas and disease activities. In the present study, we measured IL-6, IL-8 and IL-10 in the bronchoalveolar lavage fluid(BALF) from patients with pulmonary sarcoidosis to find out whether there is an imbalance between proinflammatory cytokines and antiinflammatory cytokines in the lung. Methods: Fourteen subjects with the diagnosis of sarcoidosis and six healthy volunteers were included. BALF was concentrated ten-fold by pressure ultrafiltration and each cytokine levels were measured by EUSA method. Active sarcoidosis was defined by major organ involvement or clinically progressive diseases. Results: The mean IL-6 levels in the BALF of the active sarcoidosis group were significantly increased than in controls or inactive sarcoidosis group(p<0.05). Meanwhile, the IL-8 levels were increased and IL-10 levels were decreased in the active sarcoidosis group than in controls or inactive sarcoidosis group without significance(p>0.05). In active pulmonary sarcoidosis patients, the IL-6 levels in BALF correlated with the BALF CD4/CD8 ratio(r=0.768, p<0.05) and IL-8 levels(r=0.564, p<0.05). Conclusions : The data presented showed that pro-inflammatory cytokine IL-6 is important in the pathogenesis of sarcoidosis and decreased tendency of anti-inflammatory cytokine IL-10 might also be involved in the development of granulomatous inflammation in sarcoidosis.

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