• KSBB Journal
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• v.6 no.1
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• pp.9-14
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• 1991

We studied the production and excretion of alpha-interferon in recombinant Escherichia coli harboring plasmid pIF-III-B, which carries alpha-interferon gene under the control of lipoprotein and lacUV5 promoter, and lac operator. Basically, the effects of concentrations of ampicillin and an inducer, IPTG, for the expression of the cloned gene, on the productions of alpha-interferon and plasmid stability were studied. The highest production of alpha-interferon was observed at 50 mg/1 of ampicillin concentration and 0.5 mM of IPTG. The plasmid pIF-III-B was maintained very stably in medium with ampicillin but segregated rapidly in medium without ampicillin. Also, the plasmid was segregated more rapidly in medium with an inducer higher than 0.5 mM.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.79-89
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• 1998

Purpose: Though many antiviral or immunomodulatory agents have been used in patients with chronic HBV hepatitis, interferon is considered to be the only effective therapeutic agent so far. Among immunomodulatory agents, thymodulin, the oral form of thymosin, is currently in clinical trial. We compared the efficacy of alfa-interferon therapy alone with a combined therapy of alfa-interferon and thymodulin in children with chronic active hepatitis B. Method: Twenty three children aged 4.4~13.7 years who were known to be positive for HBsAg and HBeAg in serum for at least 6 months and who had biopsy-proven chronic active hepatitis were given either combined therapy of alfa-interferon and thymodulin or alfa-interferon alone, and all children were HBV DNA positive in their serum at the beginning. Follow-ups have been done for at least 1 year after a 6 month course of therapy and clearance of viral replication markers has been evaluated. Results: 1) During follow up period, 11 (48%) children were seroconverted to anti-HBe and were cleared of HBV DNA from their serum. However, 2 of them relapsed after discontinuance of interferon therapy. 2) Seroconversion occurred more frequently among those who had not been vertically transmitted, had elevated serum ALT levels and low HBV DNA levels before interferon therapy. 3) There was no significant advantage of the combined therapy with thymodulin compared to interferon therapy alone. Conclusion: Combined therapy of alfa-interferon and thymodulin failed to demonstrate synergistic effect. We think that combination therapies of alfa-interferon with other antiviral or immunomodulatory agents need to be studied in order to achieve better therapeutic responses.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.74-92
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• 2005

Objectives/Methods : To analyze the effect of Injinchunggantang(IJCGT) to Interferon-${\alpha}/{\beta}$ signal transmission system in HepG2 cells, HepG2 Cell were treated with IJCGT. Also, revelation of MxA, 2'5'-OAS mRNA leaded by Interferon-${\alpha}/{\beta}$ and revelation and activation of Jak1, TYK1, and STAT 1, all main signal transmission factors, were analyzed. Results : The analysis resulted in the following 1. With interferon ${\alpha}/{\beta}$ there was no affect cell propagation of Hep G2 cells. With IJCGT alone, cell propagation of HepG2 was promoted, and cell propagation control function was recovered. 2. With interferon ${\alpha}/{\beta}$ cell death was unaffected. With IJCGT apoptosis of HepG2 cell was restrained, and the cell's reaction to interferon was unaffected. 3. With interferon ${\alpha}/{\beta}$ treatment mRNA revelation of MxA and 2'5'-OAS was induced. When HepG2 cells were injected with IJCGT without interferon ${\alpha}/{\beta}$ treatment, mRNA revelation of MxA and 2'5'-OAS increased in proportion to the treatment density. With pre-treatment of IJCGT, leaded with interferon ${\alpha}/{\beta}$, promoted revelation of MxA, 2'5' -OAS mRNA. 4. Though mRNA revelation of lakl, TYK1 and STAT1 was unaffected with IJCGT, activation of STAT1 was promoted with an increase of phosphorylation of STAT1 protein. With pre-treatment of IJCGT, Jak1, TYK2, STAT1 phosphorylation, leaded with interferon, strengthened. 5. TNF-a, IL-1b and LPS present, revelation of MxA and 2'5'-OAS mRNA leaded by interferon was restrained when HepG2 cells were treated with IJCGT, and the interferon signal transmission system restraint action leaded by inflammatory cytokines was moderated. Conclusion : These results support a role for IJGCT in promotion of anti-virus action through maintainance of the liver's sensibility toward interferon. A clinical study of an interferon treated patient treated also with IJGCT is needed to determine its efficacy.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.637-644
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• 1996

Interstitial pneumonitis associated with interferon alpha therapy for chronic hepatitis C was first describe6 in 1994 by Kazoo et al In Japan. The mechanism of interstitial pneumonitis developed by interferon alpha was still unknown but immunologic, allergic of direct lung toxicity were suggested. We experienced a case of interstitial pneumonitis developed during interferon alpha therapy for chronic hepatitis C in a 52-year-old male patient. He was treated with 6 million units of interferon alpha intramuscularly 3 times per week for 4 weeks and noted progressive dyspnea and cough. These symptoms were subsided after 6 weeks' discontinuation of interferon alpha therapy. And so, he was retreated with 3 million units of interferon alpha 3 times per week for 8 weeks and felt dyspnea again. He was admitted to our hospital for further evaluation of progressive dyspnea. Arterial blood gas(ABG) values were $PaO_2$ 90.7 mmHg and $PaCO_2$ 31.9 mmHg, and antinuclear antibody(ANA) was negative. A chest X-ray film revealed diffuse reticulo-nodular shadows in bilateral lung fields, suggesting a diagnosis of interstitial pneumonitis. A marked increase in lymphocyte count and suppressor T cell were observed in bronchoalveolar lavage(BAL) fluid. Lymphocyte stimulation test with interferon alpha was positive. Interstitial pneumonitis was confirmed by transbronchial lung biopsy. After discontinuation of interferon alpha, we gave oral steroid in the condition that clinical symptoms were being improved gradually.

• Journal of Yeungnam Medical Science
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• v.10 no.1
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• pp.190-196
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• 1993

The prognosis of chronic hepatitis C is very variable. In some, the disease is progressive and cirrhosis can develop from chronic hepatitis C. Hepatitis C virus(HCV) may act as a trigger towards hepatocellular carcinoma in patients with cirrhosis. Interferon has been used for the treatment of chronic hepatitis C in abroad, 16 patients with chronic C liver disease were treated with ${\alpha}$-interferon (alfa-2b; "Intron A" Schering Corp. Kenilworth. NJ). All patients were given ${\alpha}$-interferon in subcutaneous doses of 3 million units three times weekly for 1 to 9 months. During therapy, CBC and ALT levels were checked weakly to monthly. After therapy, patients were followed for 1 to 8 months. Among 16 patients treated with ${\alpha}$-interferon, progressive decrease of ALT levels was observed in 14(87.5%). In 11 patients(68.8%), ALT levels fell into the normal range during therapy, and in 9 of 11, within one month after therapy, 6 months after the completion of therapy in 4 of 9 patients(44.4%) whose ALT levels were in the normal range, ${\alpha}$-interferon seems to have effect in controlling disease activity in patients with chronic hepatitis C. But the changes in the usage of ${\alpha}$-interferon, dose and duration, long term follow up and more convenient and simple tests for HCV detection are recommended for the better effect and the exact evaluation on the effect of ${\alpha}$-interferon therapy in patients with chronic hepatitis C.

• BMB Reports
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• v.29 no.4
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• pp.365-371
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• 1996

Partially reduced interferon-a ($IFN-{\alpha}$) was cross-linked with thymosin ${\alpha}1$ ($T{\alpha}1$) using sulfo-succinimidyl (4-iodoacetyl) amino benzoate (SIAB), a bifunctional cross-linking reagent. The partially reduced $IFN-{\alpha}$ optimal for the cross-linking reaction was obtained by incubating native $IFN-{\alpha}$ with 0.5 mM DTT at $30^{\circ}C$ for 60~100 min. $T{\alpha}1$ was activated by incubating with sulfo-SIAB at $37^{\circ}C$ for 30 min to produce $T{\alpha}1-IAB$. The $T{\alpha}1-IFN-{\alpha}$ cross-linking was achieved by the reaction of the partially reduced $IFN-{\alpha}$ with $T{\alpha}1-IAB$. This cross-linking was between the sulfhydryl group of Cys1 in $IFN-{\alpha}$ and the N-terminal amino group of $T{\alpha}1$ through acetyl amino benzoate as a spacer. The immunological activity of the cross-linked molecule showed the same extent as that of $T{\alpha}1$, and most of the antiviral activity was retained compared to that of the partially reduced $IFN-{\alpha}$.

• YAKHAK HOEJI
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• v.53 no.3
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• pp.101-106
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• 2009

Recombinant interferon alpha-2a is an active formula for the treatment of various cancer cells like malignant melanoma and a variety of virus infection diseases like acute or chronic hepatitis. The bioassay system based on the measurement of virus inhibitory activity by interferon has been used for interferon analysis with low repeatability. Here, we developed the HPLC assay to measure reproducibly interferon alpha-2a protein content which is replaceable to the reported bioassay. This method separated interferon alpha-2a from its oxidized forms and human serum albumin used as excipients. The regression coefficient using interferon alpha-2a EP CRS is more than 0.9 in the range from 5 ${\mu}g/ml$ to 200 ${\mu}g/ml$. The recovery result in the range from 15 ${\mu}g/ml$ to 60 ${\mu}g/ml$ is $97{\sim}104%$ and the precision is $0.2{\sim}1.7%$. The interferon alpha contents of 5 products are about 30 ${\mu}g/ml$.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.109-115
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• 2001

Background: The role of the interferon consensus sequence binding protein (ICSBP), a member of interferon regulatory factor family, in protecting against a vesicular stomatitis virus (VSV) infection has not been firmly elucidated. Thus, it was investigated utilizing the human promyelocytic leukemia HL-60 cells which do not express ICSBP. Methods: HL-60 cells were stably transfected with plasmid containing cDNA for either ICSBP or DNA binding domain (DBD) and tested for their VSV-susceptibilities. The susceptibility of each transfectant group to a VSV infection was determined by a plaque assay at 1 h, 24 h, and 48 h post-infection in the presence (500 IU/ml) or absence of interferon ${\alpha}$ ($IFN{\alpha}$). Results: In the absence of $IFN{\alpha}$, the three groups showed similar sensitivities to a VSV infection. However, when pre-treated with IFN, the viral titers in both the ICSBP and control clones steadily decreased over 48 h of incubation, indicating the existence of $IFN{\alpha}$-mediated protection against VSV infection. The $IFN{\alpha}$-treated ICSBP clones appeared to be more resistant to infection compared with the control clones, although the difference was not great. On the contrary, the viral titers in the $IFN{\alpha}$-treated DBD clones increased at 24 h then decreased by 48 h. Conclusion: The expression of truncated ICSBP (DBD) does not appear to underlie the impaired protection against a VSV infection in the DBD clones, since even the control clones lacking ICSBP were protected from a VSV infection. This suggests that ICSBP does not play a critical role in the $IFN{\alpha}$- mediated anti-VSV response of HL-60 cells, although it appears to confer some resistance to a VSV infection.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.131-131
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• 1993

위암의 화학요법 성적이 만족스럽지 못하므로 기존의 항암제와 alpha-interferon을 병용사용하므로써 상승적 항암효과가 있는가를 연구하였다. R-25 flask에 위암세포주 SNU-1 및 SNU-16을 배양하면서 항암제 5-FU 혹은 cisplatin에 alpha-interferon 2A(제일제당)를 분자량의 비에 따라 병요처리하였다. 96시간 배양후 cytotoxicity를 Mosman의 방법에 따른 MIT방법으로 분석하였으며, 이를 Chou등의 combination index 분석 program을 처리하였다. 위암세포주 SNU-1에 대하여 5-FU와 alpha-IFN은 상승작용을 보였다. 5-FU의 $IC_{50}$/가 14.25$\mu$M 이었고 IFN처리시는 $IC_{50}$/가 0.02$\mu$M이었으며 combination index(CI)는 모든 용량에서 1이하였다. SNU-16에 대하여도 5-FU와 alpha-IFN의 병용사용은 상승적 작용을 나타내었다. (CI<1.0). cisplatin과 alpha-IFN의 병용시에는 CI가 1이상을 나타내어 상승작용을 증명할 수 없었다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.6 no.2
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• pp.152-160
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• 2003

Purpose: We compared the therapeutic efficacy of low dose with that of standard dose of interferon (IFN) treatment and also compared the first IFN treatment with retreatment. Methods: We have studied 51 children (age, 2~14) treated for chronic hepatitis B from March 1990 to August 1999. Twenty seven children had been treated with $3\;MU/m^2$ ($2.66{\pm}0.66\;MU/m^2$) of IFN-${\alpha}$ three times a week for 6 months (range, 6~12 months), whereas 24 children with $6\;MU/m^2$ ($4.45{\pm}0.94\;MU/m^2$). There was no significant difference in gender, age, initial ALT and HBV DNA levels between each comparative group. Results: Among the 27 children treated with $3\;MU/m^2$ of IFN, ALT level had normalized in 11 children (41%) and anti-HBe seroconversion occurred in 9 children (33%) one year after the initiation of treatment. In comparison, among the 24 children treated with $6\;MU/m^2$ of IFN, ALT normalized in 12 children (50%) and anti-HBe seroconversion occurred in 7 children (29%). In comparing the first treatment group to retreatment group, ALT level had normalized in 23 children (45%) and anti-HBe seroconversion occurred in 16 children (31%) among the 51 children treated with the first course of IFN treatment. In comparison, ALT normalized and anti-HBe seroconversion occurred in 3 children (25%) among the retreated 12 children. Conclusion: There was no significant difference in the therapeutic efficacies between $3\;MU/m^2$ and $6\;MU/m^2$ dose of IFN treated groups in ALT normalization and anti-HBe seroconversion. The retreatment efficacy of IFN-${\alpha}$ was as effective as the first treatment.