Effects Of Recombinant Human Interferon Research Articles

Observation of the Curative Effect of Recombinant Human Interferon α2b Gel Combined with LEEP Knife in Cervicitis Caused by IUD and The Effect of Copper/Low-Density Polyethylene Nanocomposite IUD

In this study, we explored the curative effect of recombinant human interferon α2b gel combined with a loop electrosurgical excision procedure (LEEP) knife to treat cervicitis. We also analyzed the clinical applications of a copper/low-density polyethylene nanocomposite intrauterine device (IUD). We selected 62 patients with IUD-induced cervicitis admitted to our hospital from March 2020 to December 2022 and divided them into experimental and control groups according to the random number table method (n = 31/group). The control group was treated with recombinant human interferon α2b gel only, while the experimental group was treated using a combination of the gel and LEEP knife. We compared the total efficacy rate of both treatments by recording the serum inflammatory cytokines levels, hospitalization, and vaginal drainage times before and after three months of treatment. We selected 50 married women of childbearing age who came to our hospital voluntarily to receive IUDs during the same period and randomly divided them into two groups (n = 25/group). Each group was administered either a copper/low-density polyethylene (Cu/LDPE) nanocomposite intrauterine device (IUD) or a TCu220C IUD. We conducted follow-ups at three, six, and 12 months after the implantation and analyzed the clinical and side effects. We observed that the total efficacy rate of the cervicitis treatment in the experimental group was 93%, 72% higher than in the control group. After six months of treatment, the tumor necrosis factor-α (TNF-α), hypersensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) levels, and the leukocyte counts of both groups were lower than that before treatment, with the test group showing lower values than the control group. Simultaneously, the hospitalization and vaginal discharge times of the experimental group were lower than those of the control group. We also followed up on the two different IUD groups after three, six, and 12 months. Compared with TCu220C IUD, the Cu/LDPE nanocomposite IUD group showed lesser side effects, such as uterine bleeding and abdominal pain. There was no significant difference between the hemoglobin levels of both groups before and after IUD insertion. In conclusion, recombinant human interferon α2b gel combined with a LEEP knife is effective in treating cervicitis patients and can control the levels of inflammatory factors in the body. This treatment was safer and quicker and shortened the vaginal discharge time. Additionally, the clinical acceptance of Cu/LDPE nanocomposite IUD for human intrauterine contraception is good due to the low occurrence of adverse reactions, such as uterine bleeding and pain. Therefore, it should be promoted in clinical gynecological practice.

Clinical Effect of Recombinant Human Interferon on Cervical HPV infection

Clinical Effect of Recombinant Human Interferon on Cervical HPV infection

HPV11 E6 mutation by overexpression of APOBEC3A and effects of interferon-\u03c9 on APOBEC3s and HPV11 E6 expression in HPV11.HaCaT cells

BackgroundCondyloma acuminatum, infected by low-risk human papillomaviruses (e.g., HPV6 and HPV11), is one of the most widespread sexually transmitted diseases. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 proteins (APOBEC3s, A3s) are cellular cytidine deaminases acting as antiviral factors through hypermutation of viral genome. However, it remains unknown whether A3s results in HPV11 gene mutations and interferon-ω (IFN-ω) exhibits antiviral activities through the A3s system. Here we investigated whether enhanced APOBEC3A (A3A) resulted in the E6 gene mutations and explore the effects of recombinant human interferon-ω (rhIFN-ω) on A3s/E6 expression in HaCaT keratinocytes containing the genome of HPV 11 (HPV11.HaCaT cells).MethodsA3A-overexpressed HPV11.HaCaT (A3A-HPV11.HaCaT) cells were established by lentiviral infection and verified by immunofluorescence and western-blotting. Cell cycle, E6 gene mutations, APOBEC3s/E6 gene expression and subcellular localization were detected by FACS, 3D-PCR and sequencing, qRT-PCR and immunofluorescence respectively.ResultsThe results suggested that A3A-HPV11.HaCaT cells were successfully established. Enhanced A3A induced S-phase arrest, G > A/C > T mutations and obvious reduction of E6 mRNA expression. A3A/A3B mRNA expression was up-regulated at 6 h and 12 h and obvious A3A staining existed throughout HPV11.HaCaT cells after rhIFN-ω treatment. RhIFN-ω could also inhibit mRNA expression of HPV11 E6 significantly.ConclusionsEnhanced A3A repressed HPV11 E6 expression through gene hypermutation, and rhIFN-ω might be an effective agent against HPV11 infection by up-regulation of A3A.

Epithelial Cells Secrete Interferon-γ Which Suppresses Expression of Receptor Activator of Nuclear Factor Kappa-B Ligand in Human Mandibular Osteoblast-Like Cells.

Prostaglandin (PG)E2 accumulates in inflamed periodontal tissue and induces receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK-osteoprotegerin (OPG) signaling associated with bone resorption. Although oral epithelial cells maintain tissue homeostasis, the role of these cells in RANKL regulation remains unknown. To mimic an inflamed condition, RANKL upregulation in human mandibular osteoblast-like cells (HMOBs) were stimulated with PGE2. Effect of recombinant human interferon (IFN)-γ or epithelial-derived IFN-γ in constitutively released or Porphyromonas gingivalis lipopolysaccharide (PgLPS)-stimulated epithelial supernatant was investigated in HMOBs. Some HMOBs were pretreated with an anti-IFN-γ antibody before PGE2 stimulation. THP-1 human monocytes and HMOBs were cocultured in a transwell system to investigate RANKL-driven THP-1 osteoclastic activity. PGE2 significantly increased RANKL messenger RNA (mRNA) and protein in HMOBs in a dose-dependent manner, while OPG protein remained similar to baseline. Epithelial cells constitutively released IFN-γ, which was substantially increased by PgLPS. HMOBs treated with epithelial supernatant or recombinant IFN-γ, concurrently with PGE2 stimulation, reduced RANKL, but not OPG, expression. In contrast, anti-IFN-γ antibody reversed the effect of epithelial mediators on RANKL expression. When cocultured with THP-1, RANKL released by PGE2-stimulated HMOBs is adequate to drive THP-1 differentiation as osteoclastogenic gene expression and bone resorption pit are increased. However, recombinant IFN-γ, or IFN-γ derived from oral epithelial cells, suppressed RANKL expression at both the mRNA and protein level, resulting in decreased THP-1-derived osteoclastic activity. Oral epithelial cells interact with HMOBs by releasing IFN-γ to regulate RANKL expression and contribute to osteoclastogenesis.

Effects of human recombinant alpha-2b interferon and feline recombinant omega interferon on in vitro replication of feline herpesvirus-1

To evaluate the effects of recombinant human interferon alpha-2b (rHuIFN-alpha2b) and recombinant feline interferon omega (rFeIFN-omega) on in vitro replication of feline herpesvirus (FHV)-1. Cultures of Crandell-Rees feline kidney (CRFK) cells. CRFK cells were treated with rFeIFN-omega or rHuIFN-alpha2b at concentrations ranging from 100 to 500,000 U/mL. Cultures were then inoculated with FHV-1. Constant concentrations of interferon products were maintained throughout the study. Reductions in the number and size of plaques were used as indicators of antiviral activity. Six plaque reduction assays were performed in duplicate. A 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay was used to detect cytotoxic effects of interferon. A 1-way ANOVA and Dunnett test were used to determine significant differences. Treatment with rFeIFN-omega at various concentrations resulted in significant reductions in the number of plaques (100,000 U/mL, 54.7%; and 500,000 U/mL, 59.8%) and in plaque size (100,000 U/mL, 47.5%; 250,000 U/mL, 81.0%; and 500,000 U/mL; 70.5%). Treatment with various concentrations of rHuIFN-alpha2b resulted in a significant reduction in plaque size (100,000 U/mL, 56.0%; 250,000 U/mL, 75.7%; and 500,000 U/mL, 69.0%). None of the tested concentrations of interferon caused significant cellular toxicosis. At some of the higher concentrations, the antiviral effect of rFeIFN-omega was greater than the antiviral effect of rHuIFN-alpha2b. Reduction in plaque size appeared to be a good indicator of the antiviral activity of interferon against FHV-1.

Effect of recombinant human interferon α B/D (rHu-IFN-α B/D) in combination with acyclovir in experimental HSV-1 encephalitis

The efficacy of recombinant human interferon α B/D in experimental HSV-1 encephalitis was investigated in the murine system. Recombinant Hu-IFN-α B/D significantly reduced the mortality in a mouse encephalitis model (about 30%, P=0.021), whereas natural mouse interferon was inactive. Combination of acyclovir with Hu-IFN-α B/D had an additive effect.

The effect of recombinant human interferon α [formula omitted] compared to interferon α 2b on SIV infection in rhesus macaques

The model of simian immunodeficiency virus (SIV) infection in rhesus macaques was used to evaluate the effects of recombinant human interferon α, Hu IFN-α 2b and Hu IFN-α B D , at two doses. Administration began 1 day prior to infection and was continued for 90 days postinfection. Both interferons suppressed SIV antigenemia during the treatment period. Following treatment animals were monitored for 4 years for rate of disease progression. Neither IFN prolonged the asymptomatic period or survival.

Recombinant interferon-gamma preserves human granulocyte bactericidal and chemoluminescence activities.

The effects of recombinant human interferon (IFN)-gamma on functions of human granulocytes (PMNL) were investigated. Incubation with IFN-gamma for up to 24 h enhanced the chemoluminescent (CL) response of polymorphonuclear leukocytes (PMNL) to Staphylococcus aureus, FMLP, opsonized zymosan, and PMA in a dose-dependent fashion for concentrations of 1-1000 units/mL. Short exposures to tumor necrosis factor (TNF)-alpha also enhanced the CL responses of PMNL, but the effects IFN-gamma and TNF alpha together, at the concentrations used, were less than additive. Incubation of PMNL for 8 h with IFN-gamma preserved their bactericidal capabilities relative to control PMNL incubated for the same length of time without IFN-gamma. Preservation of neutrophil function may be a subtle but important role for IFN-gamma.

1006 Effects of recombinant human interferon α on rat hypothalamic preoptic neurons studied by whole cell slice patch clamp method

1006 Effects of recombinant human interferon α on rat hypothalamic preoptic neurons studied by whole cell slice patch clamp method

Effect of interferon alpha‐2b in advanced multiple myeloma

The antitumour effect of recombinant human interferon (rh-IFN) alpha-2b was studied in 22 patients with advanced multiple myeloma (MM). Nine of 14 evaluable cases were refractory to cytostatic therapy; five were in relapse. rh-IFN was administered s.c. three times per week, in escalating doses starting with 2 x 10(6) IU m-2 and if possible up to 15 x 10(6) IU m-2. Two patients (one refractory, one relapsing) showed a partial response, defined as a 50% reduction of the serum M-component. Three further patients had a minor, significant but short-lived response. Subjective side-effects grade 1-2 were noted during rh-IFN therapy in all patients. In three cases thrombocytopenia necessitating platelet transfusions occurred. Although a fraction of patients with advanced MM obviously respond to rh-IFN, this type of therapy may be more effective, alone or in addition to chemotherapy, in patients with a low tumour cell burden.

Essential amino acid deprivation induces monocytic differentiation of the human HL-60 myeloid leukemia cell line

In this study we examine the effects of amino acid deprivation on the growth and differentiation of the human HL-60 myeloid leukemia cell line. The HL-60 cell line was chosen for study because of its ability to differentiate along either a granulocytic or monocytic pathway under appropriate culture conditions. Differentiation was determined by changes in cell morphology, nonspecific esterase (NSE) content, hydrogen peroxide (H2O2) production, and expression of the cell surface differentiation antigens LeuM3 (CD14) and OKM1 (CD11). Using a model system in which HL-60 cells were cultured in medium that selectively lacked one amino acid (AA), it was seen that deprivation of HL-60 cells for essential (but not nonessential) AAs results in decreased cell growth and viability and in differentiation of 30% to 60% of the surviving population of cells specifically along the monocytic pathway. This differentiation is irreversible as well as time- and dose- dependent. Culture of HL-60 cells in essential AA-deficient medium potentiated the differentiative effects of recombinant human interferon- gamma (IFN-gamma), recombinant human tumor necrosis factor (TNF), and dihydroxyvitamin D3 (D3), all of which have previously been shown to induce monocytic differentiation of HL-60 cells. Differentiated cells had decreased DNA and RNA synthesis, but protein synthesis was unchanged compared with control cells. The protein synthesis inhibitor cycloheximide prevented differentiation, indicating the necessity of protein synthesis in this process. Cell cycle analysis revealed that an increased proportion of cells cultured in AA-deficient medium was arrested in G0-G1 (80% and 50% for AA-deficient and control cells, respectively). These results suggest that alterations of AA metabolism and subsequent perturbations in DNA and RNA synthesis may be important in initiating differentiation or in augmenting cytokine-induced differentiation of HL-60 cells into more mature, nonreplicating, monocyte-like cells.

Antitumor effect of combined intraperitoneal administration of human recombinant interferon-beta and interferon-gamma against intraabdominal carcinomatosis in nude mice.

The development of useful therapy for intraabdominal carcinomatosis originating from gastrointestinal cancer is an important theme in cancer therapy. We developed recently an experimental model of intraabdominal carcinomatosis in nude mice by intraperitoneal transplantation of human colon cancer cells (RPMI 4788). Using this model, we investigated the antitumor effects of recombinant human interferon (rIFN)-beta and rIFN-gamma administered singly or in combination. Treatment was initiated 2 days after CD-1 nude mice were inoculated intraperitoneally with 5 X 10(6) RPMI 4788 cells. Intraperitoneal administration for 10 consecutive days of either rIFN-beta (2.5 X 10(5) IU/mouse/day) or rIFN-gamma (2.5 X 10(5) JRU/mouse/day) resulted in a significant prolongation of survival compared with the saline control group [survival in the control: 41.8 +/- 5.6 days (mean +/- SD)]. Combined administration of rIFN-beta and rIFN-gamma for 10 days yielded a marked synergistic effect on the prolongation of survival (114.0 +/- 8.2 days). However, combined administration of rIFN-beta and rIFN-gamma in a single dose equal to the total dose given fractionally over 10 days did not yield a synergistic effect. These results suggest that daily administration of rIFN-beta and rIFN-gamma combined may provide a highly potent antitumor effect against human peritoneal carcinomatosis.

Antiproliferative Effects of Interferons against Human Bladder Carcinoma Cell Lines in vitro

In order to evaluate the antiproliferative effects of recombinant human interferon-gamma 2c (rHu IFN-gamma 2c), recombinant human interferon-gamma (rHu IFN-gamma), natural interferon-beta (IFN-beta), and their combination with cytotoxic agents, 17 different human bladder carcinoma cell lines were tested in vitro. The antiproliferative effects were compared in evaluating the tumor cell inhibiting potency of the different interferon (IFN) classes. It could be demonstrated that interferons have inhibiting effects on the bladder cancer cell multiplication rate, yet there are significant differences in the susceptibility of different IFN preparations on different cell lines. The cell lines BT1, RT4, EJ, 468P, 253J, SD, TCCSUP, and SW1738 can be defined as sensitive, T24, 647V, VM-CUB2, and J82 as semisensitive, HT1376, 5637, VM-CUB1, 639V and SW1710 as resistant upon treatment with IFN. The combination of rHu IFN-alpha 2c, IFN-beta, and rHu IFN-gamma seems to be more effective than treatment with rHu IFN-alpha 2c alone. The cytotoxic effect of doxorubicin on bladder cancer cells can be intensified by combining it with IFN.

Effect of recombinant human interferon gamma against human cytomegalovirus.

Escherichia coli-derived human interferon-gamma (rIFN-gamma) inhibited the replication of human cytomegalovirus (HCMV) synergistically when combined with IFN-alpha. The induction of HCMV DNA polymerase was inhibited in rIFN-gamma-treated cells. It is suggested that the induction of 2-5 A synthetase does not play an important role in the anti-HCMV actions of IFNs.

Augmentation of antibody-dependent cellular cytotoxicity of polymorphonuclear leukocytes by interferon-gamma: mechanism dependent on enhancement of Fc receptor expression and increased release of activated oxygens.

The effect of recombinant human interferon (IFN) -gamma (Met-Gln form), having the same amino acid sequence as that of natural human IFN-gamma except for the N-terminal Met residue, on antibody-dependent cellular cytotoxic (ADCC) activity of human peripheral polymorphonuclear leukocytes (PMNs) against anti-chicken red blood cell (CRBC) immunoglobulin G (IgG) -coated CRBC was investigated comparatively with those of natural human IFN-alpha and -beta in vitro. IFN-gamma dramatically induced the ADCC activity at all doses tested when examined at a 1/104 dilution rate of the IgG, while no significant induction was observed with IFN-alpha or-beta. The Fc receptor (FcR) analysis by flow cytometry using fluorescein isothiocyanate-labelled (FITC) -anti-CRBC IgG revealed that IFN-gamma but not IFN-alpha or-beta remarkably increased the number of PMNs bearing FcR. By applying an in vitro measurement system for activated oxygen species using luminol solution, it was demonstrated that activated oxygen species were actually released from PMNs in the ADCC reaction. Further, inhibition experiments using three oxygen scavengers (superoxide dismutase, catalase and dimethyl sulfoxide) demonstrated the involvement of superoxide anion and hydroxy radical as cytolytic mediators in the PMN-ADCC activity induced by IFN-gamma.These results indicate a much more potent PMN-activating ability of IFN-gamma than IFN-alpha or-beta and involvement of a mechanism dependent on the enhancement of FcR expression on the PMN surface and the increased release of superoxide anions and hydroxy radicals in the PMN-ADCC augmentation by IFN-gamma.

Effect of interferon on activated oxygen production in human monocytes in vitro : Direct measurement of phagosomal activated oxygens by a new method using luminol-binding microspheres.

We examined the effects of recombinant human interferon (IFN)-gamma, having Met-Gln at the N-terminal, on the in vitro production of phagosomal and extracellular activated oxygen species by human monocytes after phagocytosis and compared the results with those for natural human IFN-alpha and -beta. The phagosomal production was measured by a new method using luminol-binding microspheres and the extracellular production was measured by two conventional methods using luminol sulution and opsonized zymosan or yeast particles. We also examined the effect of the IFN-gamma on the phagocytic activity of human monocytes by using luminol-binding microspheres. It was found that IFN-gamma remarkably augmented both phagosomal and extracellular production of activated oxygen species after phagocytosis in a dose-dependent fashion. However, IFN-alpha and -beta had a weak effect on the phagosomal production only at the highest dose tested. The natural IFNs also augmented moderately or slightly the extracellular production stimulated by opsonized zymosan but not opsonized yeast particles. IFN-gamma augmented the phagocytic activity of human monocytes. THese results demonstrated that the human monocytes treated with the IFN-gamma actually produced a larger quantity of phagosomal activated oxygen species than those treated with the natural IFNs, and the extracellular production did not always reflect the phagosomal production.