• Title/Summary/Keyword: Interferon alpha-2a

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Association of Intracellular $T_H1-T_H2$ Balance in CD4+ T-cells and MIP-$1{\alpha}$ in CD8+ T-cells with Disease Severity in Adults with Dengue

  • Kadhiravan, Tamilarasu;Saxena, Ankit;Singh, Amar;Broor, Shobha;Sharma, Surendra K.;Mitra, Dipendra K.
    • IMMUNE NETWORK
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    • v.10 no.5
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    • pp.164-172
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    • 2010
  • Background: We tested the hypothesis that dengue haemorrhagic fever (DHF) is associated with a $T_H1$-skewed immune response as opposed to dengue fever (DF). Methods: We estimated intracellular (in T-cells) and serum levels of designate $T_H1/T_H2$ cytokines [interferon-${\gamma}$ (IFN-${\gamma}$), interleukin-4 (IL-4), and tumor necrosis factor-${\alpha}$] and macrophage inflammatory protein-$1{\alpha}$ (MIP-$1{\alpha}$) at admission, 48h, and day 5 in 20 adults with dengue (DF=10, DHF=10) and 10 dengue-naive healthy controls. Results: At admission, intracellular IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells and proportion of MIP-$1{\alpha}$-positive CD8+ T-cells were significantly higher in patients with DHF [7.21 (5.36~10.81) vs. 3.04 (1.75~4.02); p=0.011 and 6.2% (3.2~8.2%) vs. 2.4% (2.0~3.6%); p=0.023]. The latter showed a significant positive correlation with IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells (Spearman's rho=0.64; p=0.003), percentage-change in haematocrit (rho=0.47; p=0.048), and serum alanine amino-transferase level (rho=0.61; p=0.009). Conclusion: We conclude that DHF is associated with a $T_H1$-skewed immune response. Further, MIP-$1{\alpha}$ in CD8+ T-cells is an important immunologic correlate of disease severity in dengue.

Preliminary Studies on Production of Porcine Leucocyte Interferon (돼지 Leucocyte Interferon 생산(生産)에 대한 기초연구(基礎硏究))

  • Jun, Moo Hyung;Chung, Un Ik;Park, Bong Kyun;Kim, Kyo Joon;Lee, Hun Jun
    • Korean Journal of Agricultural Science
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    • v.12 no.1
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    • pp.153-161
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    • 1985
  • As a preliminary step for production of large quantities of porcine leucocyte interferon(Por IFN-${\alha}$), various factors such as the sources of leucocytes, inducers and culture conditions were investigated. In addition, an assay system for the potency of porcine interferon was developed in a micro-system by using porcine kidney cell line, PK-15, and vesicular stomatitis virus. By the experiments, it was found that the porcine leucocyte interferon was synthesized more effectively in the leucocyte suspension with the higher viability and the lesser erythrocyte contamination. Regarding cell sources, the peripheral leucocytes produced a consistently higher unit of interferon than the spleen cells. When the efficiency of inducers was compared, the Sendai virus at the concentration of 125 HA unit/ml was found to be more effective for porcine leucocyte interferon production than the Newcastle disease virus. Average potency of 9 batches of the crude interferon measured by the established assay system was 1,200 unit/ml.

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Effect of ${\alpha}$-Interferon 2b on Chronic Hepatitis B Patients with High Serum ALT (급상승된 혈청 ALT치를 나타낸 만성 B형 간염 환자에 대한 ${\alpha}$-Interferon 2b의 치료 효과)

  • Lee, Heon-Ju;Song, Young-Doo
    • Journal of Yeungnam Medical Science
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    • v.15 no.2
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    • pp.237-245
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    • 1998
  • 만성 B형 간염 환자에서 Interferon (IFN) 치료 후 혈청 HBeAg 소실 및 anti-HBe의 양전율을 높이고 효율적인 치료의 근거를 알기 위하여 치료 전 간기능검사상 갑자기 상승한 혈청 ALT치를 나타낸 환자군과 그렇지 않은 대조군을 대상으로 하여 IFN을 투여한 군과 IFN 치료없이 정상 HBeAg의 자연 소실을 보인 환자군을 임상적으로 장기간 관찰하고 조사하였다. ALT치가 정상 상한치의 4배 이상 높이 증가되어 3개월 이상 왕복을 보인 40명의 환자(A군)와 ALT치가 정상 상한치의 3배 이하로 증가된 10명(B군)에게 ${\alpha}$-IFN 2b를 매일 300만 단위 피하주사로 3~12개월 주사하였다. 대조군으로는 ALT치가 A군처럼 장승한 45명 (C군)이었으며, IFN 치료없이 평균 2.9년을 관찰하였다. HBeAg/anti-HBe 혈청 양전율은 A군 68%, B군 20%, C군 13%이었으며 IFN 치료 중단 후 1년까지의 HBeAg 재양성율은 A군에서 29%였고 HBeAg이 소실된 A와 B군의 38명중에서 6명에서 HBV DNA가 양성이었다. 6명중 4명은 HBeAg/anti-HBe 양전을 보였으나 HBV DNA 양성이었고 나머지 2명은 HBeAg, anti-HBe 및 HBV DNA (hybridization) 모두 음성이었으나 중합효소연쇄반응검사상 HBV DNA 양성이었다. 이상의 결과를 보면 비록 IFN 치료 후에 HBeAg이 소실되었다가 다시 양성화되더라도 IFN은 단기간내에 혈중 HBeAg이나 DNA가 자연적으로 감소가 될 환자나 그렇지 않은 환자에게도 HBV의 비증식화를 유발하여 도움이 될 것으로 사료된다. 그러나 IFN 투여 후에도 혈중 HBeAg과 DNA 소실에 전혀 도움이 되지 않을 환자 및 HBV 증식 억제효과가 기대되는 HBV 간질환 환자의 조건, IFN 투여량, 기간 등에 대한 계획적이고 체계적인 연구로 더 나은 치료효과를 기대할 수 있으리라 생각된다.

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Pharmacokinetics of DA-3021 (mono-PEGylated recombinant human interferon ($\alpha$-2a) after Subcutaneous Administrations to Experimental Animals

  • Jo, Yeong-Woo;Kim, Won-Geun;Choi, Yun-Kyu;Jeon, Hyun-Kyu;Kim, Dong-Hwan;Park, Beom-Soo;Lee, Sung-Hee;Kim, Won-Bae;Youn, Yu-Seok
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.424.1-424.1
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    • 2002
  • Interferon has therapeutic potential for a wide range of infectious and proliferative disorders such as chronic hepatitis C and malignant melanoma. However. it has some therapeutic problems as other protein therapeutics do. A variety of approaches have been developed to circumvent these problems. Among them. the attachment of a polyethylene glycol (PEG) moiety 10 interferon is considered as one of the most promising solutions for its ability of extending the plasma residence time. (omitted)

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Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2

  • Yu, Tao;Yang, Yanyan;Kwak, Yi-Seong;Song, Gwan Gyu;Kim, Mi-Yeon;Rhee, Man Hee;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.127-133
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    • 2017
  • Background: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. Methods: The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis $factor-{\alpha}/interferon-{\gamma}-treated$ synovial cells, and HEK293 cells transfected with various inducers of inflammation. Results: G-Rc significantly inhibited the expression of macrophage-derived cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$. G-Rc also markedly suppressed the activation of TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells. Conclusion: G-Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling.

Serotyping in Patients with Chronic Hepatitis C

  • Soon-Mo Chang
    • Biomedical Science Letters
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    • v.9 no.4
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    • pp.209-214
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    • 2003
  • To determine the clinical usefulness of Immuno Blot test, 160 samples from the patients with chronic HCV infection were analyzed. And serotyping and line probe assay were performed to evaluate the distribution of hepatitis C virus genotypes in Korean isolates. In this group, as a result of genotyping type 1 band 2a, the serotype I and II were the most common source of HCV infection. There were no significant difference in response to the alpha-interferon HCV infection treatment with the subtype 1 b or 2a. And the serotypes of NS4 peptides were compared with the genotypes to evaluate their clinical usefulness. Among 49 cases studied for genotypes and serotype, genotype 1 b, 1 b/2b, 2a, 2a/2c and 2b were 51.0%, 2.0%, 34.6%, 8.1% and 4.0%, respectively. The serotypes I and II were 57.1% and 42.8%, respectively; they were matched with genotypes in 85.7% and seemed to be easy to perform. To monitor their performing progress or treatment response, serotype test was made before the genotype test. The Result showed that there was no significant difference in response to the alpha-interferon HCV infection treatment with the subtype 1 b or 2a in Korea.

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Considerations in the Design of the Preclinical Safety Program for PegIntron

  • Davis, Thomas
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.87-88
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    • 2003
  • PegIntron is the pegylated form of human recombinant interferon alfa-2b (IFN${\alpha}$2b). IFN ${\alpha}$2b, known as Intron A, has been in approved clinical use since the 1980's for various cancer indications, and for the treatment of Hepatitis C. In the mid 1990's, several clinical investigators reported that combination therapy with ribavirin and Intron A dramatically increased the therapeutic efficacy for treatment of Hepatitis C.(omitted)

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Long Term Follow Up of Interferon-alpha Treatment in Children with Chronic Hepatitis B (만성 B형간염 환아에 대한 Interferon-alpha 치료결과의 장기 추적관찰)

  • Baek, Seoung-Yon;Eom, Ji-Hyun;Chung, Ki-Sup
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.6 no.2
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    • pp.140-151
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    • 2003
  • Purpose: We tried to evaluate the long term efficacy and positive predictive factors of interferon-alpha treatment in children with chronic hepatitis B. Methods: The study population included 113 children who received interferon therapy between May 1982 and July 2002 (20 years) for chronic hepatitis B in Department of Pediatrics, Yonsei University College of Medicine. Male to female ratio was 2.3 : 1 and the mean age at diagnosis was $11.1{\pm}4.1$ years old. Response to treatment was defined as normalization of alanine aminotransferase (ALT), disappearance of HBeAg and HBV-DNA Eighty two children responded while 32 did not. Interferon-alpha was given intramuscularly for 6 months at a dosage of $3{\times}10^6$ unit, 3 times weekly. In relapsed cases, lamivudine or interferon retreatment was done. Results: Seroconversion rate was 77.0% in terms of HBeAg, 74.3% in terms of HBV-DNA, and 80.5% in terms of ALT normalization after treatment. Seroconversion rate of both HBeAg and HBV-DNA was 72.6%. Analyzed by life table method, the effect of the treatment had been maintained over 10 years after cessation of therapy. Pre-treatment ALT level was the only significant positive predictive factor of response. Eleven cases (13.4%) relapsed, and 2 out of 3 showed response when treated with lamivudine and 1 out of 3 with interferon retreatment. Conclusion: Interferon-alpha showed significant efficacy in the treatment of chronic hepatitis B in our study. Further studies about the effect of interferon therapy on complications of hepatitis such as hepatocarcinoma, cirrhosis are warranted.

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Production and Characteriuation of Monoclonal Antibodies against Human Interferon-$\alpha$ (인터페론 알파에 대한 단세포 군항체의 제조 및 특성)

  • Park, Kyung-Hee;Lee, Ihn-Sook
    • The Korean Journal of Zoology
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    • v.35 no.1
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    • pp.1-7
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    • 1992
  • Seven monoclonal antibodies were produced by fusing splenocytes from Balb/C mouse immunized with partially purified human interferon-a (HUIFN-a) with NSO plasmacytoma cells. aery were identified as five IgG class (432.22: IgG2b/n, 460.52: IgG2b/a , 548.46: IgG2a/n , 573.10: IgG2b/h , 625.12: IgG2b/n ), one IgA class (460.50: IgA/n ) and one IsM class (465.27: IgA/n ), and all of them revealed highly sensitive to HUIFN- a IgG class monoclonal antibodies have pts ranged from 8.2 to 8.6. Ascites fluids produced from primed Balb/c mice and were purified through column chromatography. The cytopathic effect (CPE) inhibition assay to examine neutralization of HuIFU-a by IgG class monoclonal antibodies, gave that MAbs 460.52, 548.46, 573.10 can neutralize HUIFU- a arith varying degrees except 432.22. Therefore, it is deduced that these various monoclonal antibodies may recognize the distinct epitopes on HUIFN-a.

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Impaired Functions of Lymphocytes on Nitric Oxide Production in Endotoxin- Tolerant Mice (내독소내성 마우스에서 Nitric Oxide 생성에 미치는 림프구 부전)

  • Gil, Young-Gi;Kang, Mi-Kyung
    • Journal of Life Science
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    • v.18 no.11
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    • pp.1471-1478
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    • 2008
  • In this study, nitric oxide (NO) production in a macrophage-lymphocyte co-culture system was used to assess the cytokine producing capability of cells during endotoxin tolerance in mice. Incubation of peritoneal macrophages with interferon-$\tau$ (IFN-$\tau$) in the presence of lipopolysaccharide (LPS) augmented NO synthesis. Exogenous tumor necrosis factor-$\alpha$(TNF-$\alpha$) could also replace LPS for the stimulation of NO production. Macrophages co-cultured with splenic lymphocytes showed augmented NO synthesis by LPS alone. However, pretreatment of mice with 2.5 mg/kg LPS completely prevented the lethality and the increase of blood TNF-$\alpha$ and IFN-$\tau$ after the second challenge with a lethal dose of LPS. In addition, when macrophages prepared from LPS-tolerant mice were co-cultured with normal splenocytes, LPS also could not induce the production of NO, even in the presence of exogenous TNF-$\alpha$. Moreover, when normal macrophages were co-cultured with splenocytes obtained from LPS-tolerant mice, stimulation with LPS could not evoke the NO production enhancement. However, this down-regulation was able to reverse by exogenous IFN-$\tau$ or concanavalin A (ConA), a stimulator of IFN-$\tau$ production. Our results indicate that not only macrophages but also lymphocytes contribute to LPS tolerance. As INF-$\tau$ can enhance the expression of TNF-$\alpha$, the decrease of INF-$\tau$synthesis from lymphocytes may orchestrate with the decrease of TNF-$\alpha$ synthesis from LPS-tolerant macrophages for the production of tolerant state and the prevention of excessive inflammation. Therefore, LPS tolerance may be exploited for prophylaxis of severe sepsis in patients at risk.