• Archives of Pharmacal Research
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• v.29 no.4
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• pp.302-309
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• 2006

Lupus-like syndrome is characterized by multiple organ injuries including lungs and kidneys. Endotoxin induces a transiently intent systemic inflammatory response and indirectly transient acute lung injury in normal condition. However, whether endotoxin may trigger the persistent development of lung injury in chronic, inflammatory lupus-like syndrome compared with normal condition remains unclear. We examined the pulmonary vascular permeability and production of proinflammatory cytokines, such as TNF-${\alpha}$, IL-6, IL-10 and IFN-${\gamma}$, which play prominent roles in the pathogenesis of lupus-like tissue injury, 6 hand 72 h after i.p. lipopolysaccharide (LPS; endotoxin) injection in pristane-primed chronic inflammation ICR mice characterized by a lupus-like syndrome. These results demonstrated that levels of serum IL-6, IL-10 and IFN-${\gamma}$ and bronchoalveolar lavage (BAL) IL-6 and IFN-${\gamma}$ were remarkably increased 6 h in LPS-exposed pristane-primed mice compared with pristane-primed controls, while pulmonary vascular permeability and levels of serum and BAL TNF-${\alpha}$ were not. And levels of BAL TNF-${\alpha}$, IL-6 and IL-10 were significantly enhanced 72 h in LPS-exposed pristane-primed mice compared with pristane-primed controls. Also, LPS significantly induced the increased in vitro production of TNF-${\alpha}$, IL-6 and IL-10 by lung cells obtained from LPS-exposed pristane-primed mice compared with LPS-exposed normal mice. Our findings indicate that LPS may trigger persistent progression of lung injury through late overproduction of BAL TNF-${\alpha}$, IL-6, and IL-10 in lupuslike chronic inflammation syndrome compared with normal condition.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.910-916
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• 2002

Endotoxin tolerance reduces the capacity of monocytes to produce proinflammatory cytokines, results in cellular immune paralysis, and down-regulates the production of helper T (Th)1 type cytokines with a shift toward a Th2 cytokine response. Prostaglandin (PG)E$_2$ in the immune system also results in macrophage inactivation and the suppression of Th1 activation and the enhancement of Th2 activation. However, the inhibitory effects of PGE$_2$ on the altered polarization of the Th cell and macrophage interleukin (IL)-6 production characterized in part by cellular immune paralysis in a state of endotoxin tolerance is unclear. This study was undertaken, using indomethacin, to investigate the role of endogenous PGE$_2$ on the Th cytokines and macrophage IL-6 production in a state of endotoxin tolerance compared to those with endotoxemia mice, wherein, in this latter case, the increased production of proinflammatory cytokines and PGE$_2$ is exhibited. Endotoxemia was induced by injection of lipopolysaccharide (LPS; 10 mg/kg in saline) i.p. once in BALB/c mice, and endotoxin tolerance was induced by pretreatment with LPS (1 mg/kg in saline) injected i.p. daily for two consecutive days and then with LPS 10 mg/kg on day 4. Splenocytes or macrophages were obtained from endotoxemia and endotoxin tolerance models pretreated with indomethacin, and then cytokine production was induced by Con A-stimulated splenocytes for the Th cytokine assays and LPS-stimulated macrophages for the IL-6 assay. Our results showed that endotoxemia led to significantly reduced IL-2 and IL-4 production, to significantly increased IL-6 production, whereas interferon $(IFN)-{\gamma}$ production was not affected. Indomethacin in the case of endotoxemia markedly attenuated $IFN-{\gamma}$ and IL-6 production and didnt reverse IL-2 and IL-4 production. Endotoxin tolerance resulted in the significantly reduced production of IL-2 and $IFN-{\gamma}$ and the significantly increased production of IL-4 and IL-6. Indomethacin in endotoxin tolerance greatly augmented IL-2 production, significantly decreased IL-4 production, and slightly attenuated IL-6 production. These findings indicate that endogenous PGE$_2$ may mediate the suppressed Th1 type immune response, with a shift toward a Th2 cytokine response in a state of endotoxin tolerance, whereas endotoxemia may be regulated differentially. Also, endogenous PGE$_2$ may mediate macrophage IL-6 production in the case of endotoxemia to a greater extent than in the case of endotoxin tolerance.

• Journal of Community Nutrition
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• v.6 no.2
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• pp.103-109
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• 2004

Body antioxidant status is an important factor for the prevention of many chronic diseases in the elderly. This study was done to investigate antioxidant status and its relationship to immune response by measuring plasma cytokine (IL-2 and IL-6) levels in elderly women. Subjects were 76 elderly women aged over 60 years, visiting Jangwhi Social Welfare Center of Seongbook-Gu in Seoul. Subjects were divided into 3 groups according to age (< 65, 65 - 74, > 75). Dietary intakes were assessed by semi-quantitative food frequency questionnaires (SFFQ). Plasma vitamin C level was measured by 2,4-dinitrophenylhydrazine method and plasma levels of vitamin E, A and ${\beta}$-carotene were measured by HPLC. Plasma levels of IL-2 and IL-6 were determined with a solid phase sandwich enzyme linked-immuno-sorbent assay (ELISA) using commercial kits. The average intakes of antioxidant vitamins were 96.3mg (137.5% of RDA) for vitamin C and 523.3 ${\mu}$gRE (74.8% of RDA) for vitamin A in elderly women. All of the average plasma levels of antioxidant vitamins were within normal range. However the percentage of the elderly women with deficiency plus marginal values were 7.9% in vitamin C, 9.2% in vitamin A and 7.9% in vitamin E. Plasma levels of IL-2 and IL-6 were 27.1${\pm}$7.1pg/ml and 5.9${\pm}$5.3pg/ml in elderly women. Correlation data showed that plasma IL-2 level was negatively correlated with plasma vitamin C level. In addition, IL-6 level was also negatively correlated with plasma vitamin C, A and E levels, respectively. There was a significant positive correlation between erythrocyte thiobarbituric acid-reactive substance(TB-ARS) level and plasma IL-2 or IL-6 levels. In addition, erythrocyte TBARS level showed a significant positive correlation with plasma total antioxidant status (TAS) level and a significant negative correlation with plasma vitamin C level. Overall results might imply that the decreased levels of antioxidant vitamins result in an increase in oxidative stress and thereby increase cytokine production such as IL-2 and IL-6. However further research is required to elucidate these relationships.

• The Korea Journal of Herbology
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• v.29 no.5
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• pp.65-73
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• 2014

Objectives : The purpose of this study is to prove the effect of Gamikyejakjimo-tang (ji$\bar{a}$w$\grave{e}$igu$\grave{i}$sh$\acute{a}$ozh$\bar{i}$m-t$\bar{a}$ng, GK) on rheumatoid arthritis. Methods : We checked viability and measured production of IL-$1{\beta}$, IL-6, IL-17, TNF-${\alpha}$ in RAW 264.7 cell after treat by GK. Then we measured rheumatoid arthritis index score of DBA/1 mice with rheumatoid arthritis induced by CIA after GK oral administration, checked IL-$1{\beta}$, IL-6, IL-17, TNF-${\alpha}$ and hs-CRP tests in serum. Also we were observed mRNA expression of IL-$1{\beta}$, IL-6, IL-17 and TNF-${\alpha}$ in spleen by RT-PCR. Results : GK showed cell viability of 100% or higher in all concentration in RAW 264.7 cells. GK inhibited LPS-induced productions of rheumatoid arthritis mediators cytokine in RAW 264.7cells. GK treated group showed improvement from rheumatoid arthritis at decreased the index score. Also, GK treated group decreased level in serum of IL-1b, IL-6, IL-17, TNF-a and hs-CRP tests by 31%, 35%, 20%, 57% and 58% respectively. Finally, GK treated group showed decrease expression of IL-$1{\beta}$, IL-6, IL-17 and TNF-${\alpha}$ mRNA in spleen by 46%, 51%, 25% and 42% respectively. Conclusions : In this study, in-vitro and in-vivo results observed rheumatoid arthritis factors cytokine of IL-$1{\beta}$, IL-6, IL-17 and TNF-${\alpha}$ decrease in RAW 264.7 cells, serum, mRNA expression. Also, GK showed decrease of inflammation figure in hs-CRP tests depending on effect of rheumatoid arthritis. Thus, these results can used as a effective drug of GK for rheumatoid arthritis.

• Journal of Life Science
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• v.20 no.8
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• pp.1276-1280
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• 2010

Berberine has shown a number of beneficial effects, including anti-tumor, anti-inflammation, and vasodilatory effects. In this work we investigated the effects of berberine on the production of proinflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$, and IL-6 in mice. The supernatants of cultured splenocytes exposed with berberine or berberine plus LPS were harvested to assay TNF-$\alpha$, IL-$1{\beta}$, and IL-6. The sera from the mice injected with berberine or berberine plus LPS were then isolated to assay these cytokines. The TNF-$\alpha$ production in mice splenocyte cultures exposed to berberine was inhibited compared to the PBS control. The sera from LPS plus berberine injected mice showed lower levels of TNF-$\alpha$ compared to those of LPS only injected mice. The IL-$1{\beta}$ production in mice splenocyte cultures exposed to berberine was inhibited at a high dose (3.0 ${\mu}g/ml$) compared to the PBS control. Also, the increase of IL-$1{\beta}$ by LPS exposure in splenocyte cultures was inhibited by a high dose of berberine. The IL-6 in splenocyte culture supernatants showed lower levels after berberine compared to the PBS control. Also, production of IL-6 after LPS exposure in splenocyte cultures was inhibited by a low dose of berberine (0.3 ${\mu}g/ml$). These findings suggest the probability that berberine down-regulates the production of proinflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$, and IL-6.

• Journal of Periodontal and Implant Science
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• v.39 no.3
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• pp.359-365
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• 2009

Purpose: The purpose of this study was to investigate the ability of Mineral trioxide aggregate(MTA) to support osteoclastic differentiation from fetal rat calvarial cell. Methods: In this study, response of IL-6, RANKL, and OPG in fetal rat calvarial cells stimulated with IL-$1{\beta}$ on MTA was evaluated by ELISA and RT-PCR. Results: The results were as follows; there was no significant difference between glass and MTA at 5days. In ELISA analysis, Glass group and MTA group showed similar IL-6 expression, Glass+IL-$1{\beta}$ group and MTA+IL-$1{\beta}$ group showed similar IL-6 expression. In RT-PCR analysis, Glass group and MTA group showed similar IL-6, RANKL, OPG mRNA expression, MTA+IL-$1{\beta}$ group and Glass+IL-$1{\beta}$ group showed 3 fold increase of IL-6 and RNAKL mRNA expression when compared with MTA group. All groups showed similar OPG mRNA expression. Conclusions: MTA does not suppress cell proliferation and increase the proinflammatory cytokine that induce osteoclastogenesis. Thus, MTA is biocompatible material that could be used in various clinical conditions.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5225-5230
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• 2013

Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera ($0.29{\pm}0.54$, $0.03{\pm}0.15$ and $0.16{\pm}0.68$ vs. $0.00{\pm}0.00pg/ml$; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls ($2.34{\pm}4.35$ vs. $4.67{\pm}4.32pg/ml$; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2389-2394
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• 2016

Background: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6, IL10 are known to influence the growth & survival of the malignant clone. Aim: The objectives of the present study were to investigate the circulating levels of BAFF, IL-10 and IL-6, correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on the patients' survival. Materials and Methods: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups. Survival analysis was performed for all patients. Results: Studied markers were higher in the MM patients compared to the normal control subjects. Patients' survival was improved by high serum BAFF levels. Conclusions: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1351-1355
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• 2016

Background: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6 and IL10 are known to influence the growth and survival of malignant clones. Aim: The objectives of the present study were to investigate the circulating levels of BAFF, IL-10 and IL-6, correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on patients' survival. Materials and Methods: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups and survival analysis was performed for all patients. Results: Studied markers were higher in the MM patients compared to the normal control subjects. Patients survival was improved by high serum BAFF levels. Conclusions: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

• Journal of radiological science and technology
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• v.33 no.4
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• pp.321-326
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• 2010

To examine the radioprotective effect of algin-oligosaccharide(AOS), radiation-induced IL(interleukin)-6 in mice treated with 3 Gy whole body irradiation once were examined. In the measurement of irradiation-induced IL-6, in comparison with the irradiation control group, in both small intestine and liver tissues of the group treated with algin-oligosaccharide for 7 days prior to irradiation, was suppressed IL-6 synthesis(p < 0.001). It is considered that the protection against radiation hazard by antioxydative reaction of algin-oligosaccharide results in down control of IL-6 value in experimental groups treated with algin-oligosaccharide. In conclusion, through our study, the fact that algin-oligosaccharide has irradiation protection effects was elucidated, and simultaneously, the possibility of the use of a natural product without chemical toxicity as an irradiation protection agent was confirmed.