• Journal of Veterinary Clinics
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• v.18 no.1
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• pp.14-17
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• 2001

Recombinant interleukin-2 (IL-2) has demonstrated as an antineoplastic agent in mice and human, but the relatively low response rates observed in clinical trials. Therefore, the present study was undertaken in order to evaluate therapeutic activities of IL-2 for the establishment of therapeutic applications. At the onset of the experiment, normal C3H/HeN mice were injected with $3{\times}10^6$ RD-995 tumor cells, murine ultraviolet radiation-induced fibrosarcoma, subcutaneously. Beginning on day 25, experimental groups were treated with a 5-day course of IL-2 (subcutaneous injection of 30,000 IU every 12 hours for 5 days). The result of this experiment revealed that RD-995 tumor grew progressively in control mice. Subcutaneous IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 treated mice were observed compared with the control mice.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2395-2399
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• 2016

Background: Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Cytokines play an important role in the regulation of immune responses and defense against viral infections. Human interleukin 6 (IL6) is a multifunctional cytokine that participates in these processes. Objective: The aim of this study was to assess the IL6-174 gene polymorphism in patients with chronic hepatitis B virus (HBV) infection as compared with healthy controls in an Iranian population. Materials and Methods: Totals of 297 HBV patients and 368 control individuals were evaluated. Genomic DNA was extracted from peripheral blood and the SSP-PCR (sequence specific primer-polymerase chain reaction) method was applied for genotyping. Results: The frequencies of genotypes C/C, G/G and C/G in HBV cases were 4.7%, 34.3%, 60.9% and in controls were 12.8%, 39.7% and 47.6%, respectively. The frequencies of G and C allele in patients and controls were 78.1%, 21.9% and 67.4%, 32.6 % respectively. There was a significant difference in the frequencies of G/G genotype (CI=1.8-7.1, OR=3.47, P=0.00001) and G allele (CI=1.34-2.23, OR=1.72, P=0.0001) between HBV patients and the control group. Conclusions: These findings suggest that the IL6-174 C/G genotype and the G allele are strongly associated with susceptibility to HBV infection. Demographic information showed that most of the subjects were male (74.4%). According to high frequency of G/G genotype in male participants (63.1%) men probably are more susceptible to hepatitis than women.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4899-4906
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• 2016

Aim: To assess the diagnostic utility of serum and salivary interleukin 6 (IL-6) levels in the differential diagnosis of potentially malignant lesions and conditions (PMLs/PMCs) and oral squamous cell carcinoma (OSCC) in a high oral cancer prevalence region. Methods: After appropriate ethical clearance and informed consent, salivary and blood samples were collected from 100 participants in each group (OSCC, PMLs, and healthy controls). Serum and salivary IL-6 levels were measured by enzyme-linked immunosorbent assay and data were subjected to appropriate statistical analysis. Results: Significant differences in IL-6 concentration were noted between OSCC and PML/C patients in both serum and saliva, with salivary levels being 2 to 3 fold higher than serum values in all the groups. Receiver operating characteristic curve analysis demonstrated 96% specificity and 99% sensitivity for salivary IL-6 in differentiating PML from OSCC. Conclusions: The results of the present study suggest that the pro-inflammatory cytokine, IL-6, is elevated in the saliva of patients with OSSC compared to PMD and controls, and thus may prove to have diagnostic and/or prognostic significance.

• Journal of Microbiology and Biotechnology
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• v.33 no.7
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• pp.864-874
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• 2023

Natural killer (NK) cell dysfunctions against hepatocellular carcinoma (HCC) in a hypoxic environment. Many solid tumors are present in a hypoxic condition, which changes the effector function of various immune cells. The transcription of hypoxic-inducible factors (HIFs) in cancer cells make it possible to adapt to their hypoxic environment and to escape the immune surveillance of NK cells. Recently, the correlation between the transcription of HIF-1α and pro-inflammatory cytokines has been reported. Interleukin (IL)-6 is higher in cancers with a highly invasive ability, and is closely related to the metastasis of cancers. This study showed that the expression of HIF-1α in HCC cells was associated with the presence of IL-6 in the environment of HCC-NK cells. Blocking of IL-6 by antibody in the HCC-NK interaction changed the production of several cytokines including TGF-β, IL-1, IL-18 and IL-21. Interestingly, in a co-culture of HIF-1α-expressed HCC cells and NK cells, blocking of IL-6 increased the production of IL-21 in their supernatants. In addition, the absence of IL-6 significantly enhanced the cytotoxic ability and the expression of the activating receptors (NKG2D, NKp44, and NKG2C) in NK cells to HIF-1α-expressed HCC cells. These effects might be made by the decreased expression of HIF-1α in HCC cells through the inhibited phosphorylation of STAT3. In conclusion, the absence of IL-6 in the interaction of HIF-1α-expressed HCC cells and NK cells could enhance the antitumor activity of NK cells to HCC cells.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.79-81
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• 2008

The effects of decursinol on various models of sepsis were investigated. Intra-peritoneal pretreatment of mice with various doses of decursinol ($1{\sim}100$ mg/kg) effectively suppressed lethality induced in three mouse models of experimental sepsis, i.e., lipopolysaccharide (LPS)/D-galactosamine (GalN), high-dose LPS (20 mg/kg), and cecal ligation and puncture (CLP). Intra-peritoneal pretreatment of mice with decursinol (50 mg/kg) markedly enhanced the LPS/GalN -induced increase of plasma interleukin-10 (IL-10) levels, without affecting plasma TNF-${\alpha}$, IL-6 and IL-12 levels. These results suggest that decursinol could be effective for prevention or treatment of sepsis.

• YAKHAK HOEJI
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• v.40 no.6
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• pp.684-689
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• 1996

PALMIWON is composed of 8 oriental herbs which has been known to show some pharmacological effects in kidney, blood vessels and immune systems, and used for the treatment of kid ney disease, hypertension, nervous disease and diabetic mellitus in the Orient for a long time. Based on our previous report that PALMIWON showed different effects on immune cells and ${\beta}$-cells, the immunoreactivity of ICSA (Islet Cell Surface Antibody) with ${\beta}$-cell (RINm5F) and the cell proliferation and function of interleukin-1${\beta}$ damaged ${\beta}$-cells in the presence of PALMIWON were examined. It was observed that PALMIWON significantly inhibited the immunoreactivity of ICSA with ${\beta}$-cell, and markedly increased cell proliferation and insulin release of interleukin-1${\beta}$ damaged ${\beta}$-cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.21 no.4
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• pp.332-344
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• 1999

Cytokines are hormone-like proteins which mediate and regulate inflammatory and immune responses. Interleukin-6 (IL-6) is involved in the final differentiation of B cells into antibody-producing cells. Interleukin-8 (IL-8) is a neutrophil chemotactic factor that plays an important role in the recruitment of neutrophil to inflammatory loci. Inflammatory mediators by cells in the gingiva have been implicated in the initiation and progression of periodontitis and oral infection. The purpose of this study was conducted to investigate the effect of lipopolysaccharide (LPS), staphylococcus enterotoxin B (SEB) on production of IL-6 and IL-8 by human gingival and facial dermal fibroblasts. Primary cultured human gingival and facial dermal fibroblasts were incubated with LPS (0.01, 0.1, $1.0{\mu}g/ml$), SEB (0.01, 0.1, $1.0{\mu}g/ml$) or LPS $(0.1{\mu}g/ml)$ plus SEB $(0.1{\mu}g/ml)$. Culture supernatants were collected at 24, 48, and 72 hrs and assessed for IL-6 and IL-8 production by enzyme-linked immunosorbent assay. IL-6 production in gingival fibroblasts stimulated with LPS was higher than that with SEB. IL-6 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-6 production in facial dermal fibroblasts was increased only by stimulation with a high concentration of LPS $(1.0{\mu}g/ml)$. Its production in facial dermal fibroblasts by exposure with SEB was decreased in comparison with control, nontreated cells. Therefore, gingival fibroblasts showed higher sensitivity than facial dermal fibroblasts in response to low concentration of LPS. Also, IL-6 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-8 production in gingival fibroblasts was enhanced greatly only by stimulation of high concentration of LPS $(1.0{\mu}g/ml)$. That by exposure with SEB was increased only in 24 hrs cultivation. IL-8 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-8 production in facial dermal fibroblasts was decreased by LPS and increased only in 48 hrs cultivation by SEB. IL-8 production by double exposure with LPS plus SEB was enhanced only in 48 hrs cultivation in comparison with single exposure of LPS or SEB. therefore, IL-6 and IL-8 production were released at various quantities according to bacterial toxin applied and site of fibroblast harvested. These results suggest that gingival fibroblasts may be concerned with IL-6 and IL-8 related inflammatory response more than facial dermal fibroblasts.

• Korean Journal of Microbiology
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• v.45 no.2
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• pp.91-98
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• 2009

Infectious bursal disease (IBD) caused by the infectious bursal disease virus (IBDV) has an important economic impact on the poultry industry worldwide. This study examined the adjuvant effects of a plasmid encoding chicken interleukin-6 (pcDNA-ChIL-6) and levamisole (LMS) on in ovo prime-boost vaccination using a genetic vaccine (pcDNA-VP243) to prime in chicken followed by a killed-vaccine boost. A pcDNA-VP243 was injected into the amniotic sac alone or in combination with a pcDNA-ChIL-6 or LMS at embryonation day 18, followed by an intramuscular injection of killed IBD vaccine at 1 week of age. The chicken were orally challenged with very virulent IBDV (vvIBDV) strain at 3 weeks of age and observed for 10 days. No mortality was observed in the groups that received the pcDNA-VP243 alone and pcDNA-VP243 plus pcDNA-ChIL-6 or LMS compared to 100% mortality in unvaccinated challenge control group. However, as determined by bursal damage (the presence of IBDV RNA, B/B ratio, and lesion score), a pcDNA-VP243 alone group was superior to pcDNA-VP243 plus pcDNA-ChIL-6 or LMS groups in the protection against post-challenge. These findings suggest that in ovo priming with genetic vaccine and boosting with killed vaccine is an effective strategy for protecting chicken against vvIBDV and the addition of pcDNA-ChIL-6 or LMS did not enhance protective immunity.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.4
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• pp.670-677
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• 2020

Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized. Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated. Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (P_app; 9.7×10^-6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t_1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and C_max after oral administration (5 mg/kg) of LMT-28 were 302±209 h·ng/mL and 137±100 ng/mL, respectively. Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

• KSBB Journal
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• v.25 no.1
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• pp.11-17
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• 2010

Here, we evaluated the effect of thrombin on the interleukin-6 production induced by tumor-necrosis-factor-$\alpha$ in endothelial cells. It is well known that tumor-necrosis-factor-$\alpha$ mediates inflammatory responses by activation of nuclear factor-kappa-B in endothelial cells. Here, we showed that lower concentration of thrombin decreased the production of interleukin-6 induced by tumor-necrosis-factor-$\alpha$ and this inhibitory effect of thrombin on interleukin-6 production was mediated by interacting with protease-activated-receptor-1. In addition, phosphoinositide-3-kinase was also involved the anti-inflammatory responses by lower concentration of thrombin in endothelial cells. These results suggested that lower concentration of thrombin mediated anti-inflammatory responses by interacting with protease-activated-receptor-1 on the cell membrane and phosphoinositide-3-kinase in the cell. These findings will provide the important evidence in the development of new medicine for the treatment of severe sepsis and inflammatory diseases and good clue for understanding unknown mechanisms by which thrombin showed the pro-inflammatory or anti-inflammatory activities in endothelial cells.