• IMMUNE NETWORK
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• v.7 no.1
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• pp.31-38
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• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• Journal of Food Hygiene and Safety
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• v.15 no.1
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• pp.30-35
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• 2000

To investigate the effects of bacterial endotoxin on lipids and cytokines, and to explain the relationships between their changes, we carried out this study using experi-mentally Escherichia coli (E. coli) endotoxin-induced septicemic rabbits. The triglyceride and cholesterol concentrations in endotoxin groups were generally high (p<0.01 or 0.05) at all sampling time points (from 3hr to 24 hr), while phospholipid concentrations in endotoxin groups elevated in dose-dependent fashion at 3hr and 6hr after endotoxin injection compared to control group (p<0.05), There were significant negative correlations between lipids changes and cytokines (TNF-$\alpha$ and IL-1$\beta$) each other (p<0.05), and endotoxic rabbits having higher triglyceride of cholesterol levels shown relatively better conditions compared with others. As a result, the alterations in the lipid compositions caused by endotoxin may imply an active exhibition of the host defense mechanism rather than the disturbances of lipid metabolism.

• Journal of Nutrition and Health
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• v.37 no.1
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• pp.23-30
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• 2004

Ginger (Zingiber officinale Roscoe) has been used as a raw material in many traditional preparations since the ancient time. As a component of traditional health products, Ginger is known to be effective as appetite enhancer, anticold and anti-inflammation. This study was performed to investigate the immunomodulative effects of Ginger in mouse, using in vitro and ex vivo experiments. In vitro experiment, the mice splenocytes proliferation and three kinds of cytokines (IL-1 $\beta$, IL-6, and TNF-$\alpha$) prodution by peritoneal macrophages cultured with ethanol and water extracts of Ginger were used to indicate the immunomodulative effect. In order to elucidate the immunomodulative effects of Ginger ex vivo, water extract of Ginger was orally administrated into mice, and isolated splencytes and macrophages were used as experimental model. Ex vivo experiment, six to seven week old mice were fed ad libitum on a chow diet, and water extract of finger was orally administrated every other day for four weeks at two different concentractions (50 and 500 mg/kg B.W./day). In vitro study, the splenocytes proliferation was increased when water extract was supplemented in the range of 50-500 $\mu$l/ml concentration. In case of cytokines production, IL-1 $\beta$, IL-6 and TNF-$\alpha$ released by activated peritoneal macrophages were augmented by the supplementation of water extract of the Ginger. Ex vivo experiment, the highest proliferation of splenocytes and production of cytokines by activated peritoneal macrophages were seen in the mice orally administrated at the concentration of 500 mg/kg B.W./day. In conclusion, this study suggests that Ginger extracts may enhance the immune function by regulating the splenocytes proliferation and enhancing the cytokine prodution capacity by activated macrophages in mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.2
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• pp.99-105
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• 2018

The aim of this study is to compare the anti-inflammatory and immunological activity of different parts (bone, meat, and rind) of Yeonsan Ogye (YO). In order to evaluate cytotoxicity, MTT assay was performed. We investigated the production of nitric oxide (NO) and pro-inflammatory cytokines, such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$, in LPS-induced RAW264.7 cells. All parts of the YO showed no toxicity at concentrations of 1, 10, and $100{\mu}g/m{\ell}$. Rooster's bone, hen's bone, and rind decreased the production of NO. And rooster's bone, meat, and hen's bone also attenuated TNF-${\alpha}$ production in LPS-induced RAW 264.7 cells. In addition, all parts of the YO decreased IL-$1{\beta}$ and IL-6 production in LPS-induced RAW264.7 cells, whereas they all increased IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ production in normal RAW264.7 cells. Rooster exhibited higher immune activation and inhibitory activity on inflammation than a hen, and among different parts of the YO, bone showed the highest activity. Our results demonstrated and compared the anti-inflammatory and immunological activity of different parts of the YO. These results suggest that YO may be developed as a raw material for new health supplement food and medicine to attenuate various symptoms related to inflammation and immunity.

• Advances in Traditional Medicine
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• v.5 no.3
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• pp.188-194
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• 2005

The Angelicae dahuricae radix (ADR) has been used a traditional medicine to treat acne, erythema, headache, toothache, sinusitis, colds, and flu in Korea, Japan and China. Here, we report the effect of ADR on compound 48/80-induced ear-swelling and the phorbol myristate acetate (PMA) plus calcium ionophore A23187-induced inflammatory cytokine secretion in the human mast cell line, HMC-1. ADR dose-dependently inhibited the ear-swelling response induced by intradermal injection of compound 48/80, In vitro model, PMA plus A23187 significantly increased interleukin $(IL)-1{\beta}$, IL-8, granulocyte macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor $(TNF)-{\alpha}$ secretion compared with media control. We also show that the increased cytokines $IL-1{\beta}$, IL-8, GM-CSF, and $TNF-{\alpha}$ level was significantly inhibited by treatment of ADR. In addition, ADR partially blocked PMA plus A23187-induced extracelluar signal-regulated kinases phosphorylation. These results suggest that ADR might explain its beneficial effect in the treatment of mast cell-mediated inflammatory diseases.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.3
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• pp.91-100
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• 2010

Purpose: The purpose of this study was to investigate the effects of Prunellae Spica Water Extract(PSE) on immune response in macrophage cells. Methods: We had devided two group the one is normal group; not treated with PSE, and the other is experimental group; treated with PSE. We measured the cell viability of PSE on RAW 264.7 cells and investigated production of nitric oxide(NO) and cytokines such as interleukin(IL)-$1{\beta}$, IL-6 and tumor necrosis factor (TNF)-$\alpha$ with sample PSE. Results: 1. Cell viability of PSE on RAW 264.7 cells was significantly decreased in both 24 hr and 48 hr incubation. 2. NO production of PSE on RAW 264.7 cells was significantly increased in both 24 hr and 48 hr incubation. 3. IL-$1{\beta}$ production of PSE on RAW 264.7 cells was significantly increased under concentration over $50\;{\mu}g/m{\ell}$ in 24 hr incubation. 4. IL-6 production of PSE on RAW 264.7 cells was significantly increased under concentration over $50\;{\mu}g/m{\ell}$ in 24 hr incubation. 5. TNF-$\alpha$ production of PSE on RAW 264.7 cells was significantly increased under concentration over $50\;{\mu}g/m{\ell}$ in 24 hr incubation. Conclusion: NO, IL-$1{\beta}$, IL-6 and TNF-$\alpha$ production of PSE on RAW 264.7 cells was significantly increased. This study suggest that PSE stimulates the macrophage and enhances the immune response.

• The Journal of Korean Obstetrics and Gynecology
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• v.25 no.2
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• pp.12-22
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• 2012

Objectives: The aim of this study is to investigate immune enhancing effect of Houttuyniae Herba water extract(HW) on RAW 264.7 cell of mouse macrophages. Methods: Effects of HW on productions of nitric oxide(NO) and hydrogen peroxide($H_2O_2$) in RAW 264.7 mouse macrophages were measured. Effect of HW on production of cytokines such as interleukin(IL)-$1{\beta}$, IL-6, and tumor necrosis factor(TNF)-${\alpha}$ in RAW 264.7 cells was accessed by a multiplex bead array assay based on xMAP technology. All of results were represented P<0.05 compared to the normal. Results: 1. After 24 hr incubation, HW increased significantly NO production in RAW 264.7 cells at the concentrations of 25, 50, 100 and 200 ${\mu}g$/mL. 2. After 24 hr incubation, HW increased significantly hydrogen peroxide production in RAW 264.7 cells at the concentrations of 25, 50, 100 and 200 ${\mu}g$/mL. 3. After 24 hr incubation, HW increased significantly IL-$1{\beta}$ production in RAW 264.7 cells at the concentrations of 100 and 200 ${\mu}g$/mL. 4. After 24 hr incubation, HW increased significantly IL-6 production in RAW 264.7 cells at the concentrations of 100 and 200 ${\mu}g$/mL. 5. After 24 hr incubation, HW increased significantly TNF-${\alpha}$ production in RAW 264.7 cells at the concentrations of 50, 100, and 200 ${\mu}g$/mL. Conclusions: These results suggest that HW has immune enhancing activity related with its increasement of NO, hydrogen peroxide, IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in macrophages.

• Journal of Microbiology and Biotechnology
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• v.9 no.6
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• pp.826-831
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• 1999

${\beta}-Glucan$, one of the major cell wall components of Saccharomyces cerevisiae, is known to enhance the immune function, especially by activating macrophages. Accordingly, in an effort to develop a safe and efficient immune stimulatory agent, we prepared crude ${\beta}-glucan$ (glucan-p1) and partially purified ${\beta}-glucan$ that was free of mannoproteins (glucan-p2), and evaluated their effect on both the macrophage function and resistance to E. coli-induced peritonitis. To investigate the function of the macrophages, phagocytosis, $TNF-{\alpha}$ secretion, oxygen burst, and the expression of cytokine genes such as $IFN-{\gamma}$ and IL-12 were analyzed. Glucan-p2 markedly stimulated the macrophages with all these parameters. Glucan-p1, however, did not stimulate phagocytosis, yet it induced $TNF-{\alpha}$ secretion, oxygen burst, and the expression of $IFN-{\gamma}$ and IL-12, although less efficiently than glucan-p2. Finally, to test the in vivo protective effect of {\beta}-glucan against infection, the survival of mice from E. coli-induced peritonitis was investigated. After 24 h of the peritoneal challenge of E. coli, all of the mice treated with glucan-p2 survived whereas none survived in the control group. Glucan-p1 showed only a marginal effect in protecting the mice. These results suggest that mannoprotein-free gluean-p2, but not gluean-p1, can serve as an effective immune-stimulating agent.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.105-112
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• 2007

Background: Oxidative stress may play an important role in the pathogenesis of endotoxin-induced acute lung injury (ALI). This study evaluated the therapeutic effect of ${\alpha}$-lipoic acid, a nonenzymatic antioxidant, in a rat model of lipopolysaccharide (LPS) induced ALI. Materials and Methods: ALI was induced in Sprague-Dawley rats by instilling LPS (E.coli, 3mg/Kg) into the trachea. The rats were classified into the control, control+${\alpha}$-lipoic acid, LPS, and LPS+${\alpha}$-lipoic acid groups.The lung lavage neutrophil count, cytokine-induced neutrophil chemoattractant (CINC), lung myeloperoxidase (MPO), and cytokine concentrations (TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and IL-10) were measured at 2 h and 6 h after LPS administration. Results: The total cell and neutrophil counts of the LPS+${\alpha}$-lipoic acid groups were significantly lower than the LPS groups. The protein concentration in the BAL fluid was similar in the LPS groups and LPS+${\alpha}$-lipoic acid groups. The TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 concentrations in the BAL fluid were not decreased by the ${\alpha}$-lipoic acid treatment in the LPS treated rats. Conclusions: Although ${\alpha}$-lipoic acid decreased the level of LPS-induced neutrophil infiltration into the lung, it could not attenuate the LPS-induced ALI at the dose administered in this study.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.75-85
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• 2005

Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.