Administration Of Interferon Alpha-2b Research Articles

Safety, Immune, and Antiviral Effects of Pegylated Interferon Alpha 2b Administration in Antiretroviral Therapy-Suppressed Individuals: Results of Pilot Clinical Trial

In the pilot NCT01935089 trial, we tested whether pegylated interferon alpha2b (Peg-IFN-α2b) with antiretroviral therapy (ART) was safe and could impact HIV and immune measures in blood and in gut-associated lymphoid tissue (GALT). Twenty HIV-1+ ART-suppressed individuals received 1 μg/kg/week Peg-IFN-α2b with ART for 20 weeks, with intermediate 4-week analytical ART interruption (ATI). Safety, immune activation, HIV viral load and integrated HIV DNA in blood, and HIV RNA and DNA in gut biopsies were measured. A total of 7/20 participants experienced grade 3-4 adverse events, while 17/20 participants completed the study. Of the 17 participants who completed the study, 8 remained suppressed during ATI, while all 17 were suppressed at end of treatment (EoT). As expected, treatment increased activation of T and natural killer (NK) cells and IFN-stimulated molecule expression on monocytes in periphery. While circulating CD4+ T cells showed a trend for a decrease in integrated HIV DNA, GALT showed a significant decrease in HIV-1 RNA+ cells as measured by in situ hybridization along with a reduction in total HIV DNA and cell-associated RNA by EoT. The observed decrease in HIV-1 RNA+ cells in GALT was positively associated with the decrease in activated NK cells and macrophages. This study documents for the first time that 20 weeks of immunotherapy with Peg-IFN-α2b+ART (inclusive of a 4-week ATI) is safe and results in an increase in blood and GALT immune activation and in a significant decrease in HIV-1 RNA+ cells in GALT in association with changes in innate cell activation.

Evaluation of the effects of omega-3 & interferon alpha-2b administration on partial bladder outlet obstruction in a rat model.

Background & objectives:In bladder outlet obstruction-induced rat models, the transforming growth factor-beta (TGF-β) and collagen ratios have been shown to be increased. Increased TGF-β leads to fibrosis. In this study, the effect of omega-3 and interferon alpha-2b (IFN α-2b) was investigated on oxidative stress, inflammation and fibrosis in bladder structure in a partial bladder outlet obstruction (PBOO) rat model.Methods:A total of 35 male Wistar albino rats, weighing 300-350 g, were used in the study. The rats were randomly divided into five groups. At the end of the experimental period, bladders were harvested from all the rats, and pathological analysis of the rat bladder tissues was performed. In addition, investigations were carried out with enzymatic and non-enzymatic antioxidant systems to study the antioxidant properties of omega-3 fatty acid and IFN alpha-2b.Results:Increased bladder weight in the PBOO group, in comparison to the control group, was decreased by the administration of omega-3 and IFN α-2b (P=0.002). Significantly higher superoxide dismutase (SOD) levels were detected in group 2 in comparison to the control group. It was also detected that serum SOD, glutathione peroxidase and nitric oxide (NO) levels were significantly higher in group 2 when compared to the control group (P<0.05). In the pathologic evaluation, group 2 showed significantly increased inflammation and fibrosis compared to the control group. Omega-3 treatment significantly decreased inflammation. It was shown that IFN α-2b application partially decreased inflammation.Interpretation & conclusions:The results of the present study showed that in addition to the standard primary approaches to prevent the damage to the upper urinary tract secondary to PBOO, omega-3 fatty acid and IFN α-2b could be beneficial as adjunct treatment in clinical practice. However, this needs to be further investigated with prospective, randomized clinical trials with larger sample sizes.

THE RATIONALE FOR ALPHA-INTERFERON IMMUNOTHERAPY IN INFANTS WITH FUNCTIONAL GASTROINTESTINAL DISORDERS AND ACUTE INVASIVE INTESTINAL INFECTION

Background: Acute intestinal infections in children are a considerable medical and social problem worldwide. Immune therapy could help to reduce the frequency of post-infectious functional intestinal dysfunction in patients with comorbidities. Aim: To evaluate the efficacy of human recombinant interferon alpha-2b, administered at acute phase of an acute invasive intestinal infection to infants in the first months of age, suffering from functional bowel disorders. Materials and methods: This was an open-label, randomized (envelope method), prospective study in two parallel groups. The study included 59 infants of the first months of life, who were breastfed, had a history of intestinal dysfunction and were hospitalized to an infectious department. We studied efficacy of recombinant interferon alpha-2b administered in rectal suppositories at a dose of chromatography with measurement of short-chain fatty acids. Results: Standard treatment was ineffective in 63.3% (95% CI 43.9–80.0%) of patients. Administration of interferon alpha-2b reduced the rate of treatment failure by day 14 to 32% (95% CI 9–56%) and the risk of persistent diarrhea for more than one month to 29% (95% CI 5–53%). In those patients who were administered interferon, inflammation at days 25 to 55 was less severe and the levels of i-forms of short-chain fatty acids were lower. Conclusion: Immunotherapy with recombinant interferon alpha-2b seems to be a promising way to improve combination treatment of acute invasive intestinal infections in infants with a history of intestinal dysfunction, as it reduces the risk of post-infectious intestinal disorders.

Treatment of conjunctival squamous neoplasias with interferon alpha 2b

The classical approach to the treatment of squamous neoplasias of the ocular surface is based on surgical resection and cryotherapy. High rates of recurrence have been demonstrated if the margins are not free after the resection. Primary or adjuvant chemotherapy with mitomycin C (MMC) or 5-fluorouracil has been employed to treat these neoplasias, but severe side effects on the ocular surface have been described. Interferon (INF) alpha 2b is less toxic to the ocular surface. The experience in the treatment of conjunctiva-cornea intraepithelial neoplasia (CIN) with topical or intralesional INF alpha 2b is based on isolated cases or very short series. In this report, we review the published studies and include our personal experience. The safety and effectiveness of INF alpha 2b in the treatment of primary and recurrent cases of CIN are described. The absence of serious side effects after topical administration of INF alpha 2b leads to the recommendation of this modality of therapy for primary and recurrent cases of CIN.

Interferon-alpha-2b induced signal transduction and gene regulation in patient immune cells is not enhanced by a dose increase from 5 MU/m2 to 10 MU/m2

3026 Background: High dose interferon-alpha-2b (IFN-a) is employed as an adjuvant in melanoma patients who have had surgery for high-risk lesions. It mediates its anti-tumor effects via activation of the transcription factor STAT1 (signal transducer and activator of transcription) within host immune cells. We hypothesized that intermediate doses of IFN-a would be just as effective as higher doses in stimulating the activation of STAT1 and gene transcription in immune cells. Methods: Samples for analysis were obtained from patients with metastatic melanoma who were enrolled in a clinical trial of bevacizumab in combination with escalating doses of IFN-a (5 MU/m^2 and then 10 MU/m^2). Peripheral blood mononuclear cells (PBMCs) were procured before and 1 hour after the administration of IFN-a and analyzed for the presence of phosphorylated STAT1 (P-STAT1) and P-STAT2 by intracellular flow cytometric analysis and the induction of interferon stimulated gene (ISG) transcripts by Real Time PCR. Results: P-STAT1 in response to 5 MU/m^2 IFN-a was higher than that for the 10 MU/m^2 dose (p = 0.0617). The 5 MU/m^2 dose also led to a greater activation of STAT2 (p = 0.0388). The induction of interferon stimulated genes (ISGs; IFIT1, IFIT2, OAS3) within PBMCs was not enhanced following the increase in IFN-a dose to 10 MU/m^2 at 2 weeks although inhibitors of IFN-a-signaling (SOCS1 and SOCS3) were activated to a greater degree. In addition, microarray analysis was performed on 4 patients and revealed that only one of 36 interferon regulated genes was expressed to a greater extent following treatment with 10 MU/m^2 IFN-a as compared to 5 MU/m^2. Conclusions: These results suggest that 5 MU/m^2 of IFN-a are as effective as higher doses with respect to the induction of STAT signal transduction and ISGs within immune effector cells. No significant financial relationships to disclose.

Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma – CapRI: study protocol [ISRCTN62866759

After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation.DesignThe CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrolment.DiscussionThe aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

Treatment of early pterygium recurrence with topical administration of interferon alpha-2b

Treatment of early pterygium recurrence with topical administration of interferon alpha-2b

Livedo reticularis associated with interferon α therapy in two melanoma patients

We report two patients who developed intense livedo reticularis clearly related to the administration of interferon alpha 2b as an adjuvant therapy for melanoma. Histological studies showed scattered perivascular infiltrates without vasculitis. Laboratory tests excluded any underlying condition. Resolution of the symptoms was observed in both patients when interferon alpha was withdrawn. These cases highlight the occurrence of livedo reticularis as an uncommon side-effect of interferon alpha treatment.

Effect of single-dose administration of recombinant interferon-alpha2b on gastric myoelectrical activity in patients with chronic hepatitis C

Upper abdominal complaints during interferon therapy may result from impaired gastric motility and/or evacuatory function. We examined the effect of acute administration of interferon on gastric myoelectrical activity (GMA) with the use of surface electrogastrography. The study population comprised 25 patients with chronic hepatitis C. All of them were naive to interferon. On 2 days, after a 25-min basal GMA registration, in group A (5 men, 7 women, aged 44.3 +/- 2.8 years) placebo or 5 million i.u. recombinant interferon alpha-2b (IFNA) was administered s.c. and the GMA was recorded in the interdigestive state for two periods (2 h and 4 h), separated by a 15-min break. In group B (7 men, 6 women, aged 44.7 +/- 3.9 years) placebo or 5 million i.u. IFNA was injected s.c. after the ingestion of a semiliquid test meal of 364 kcal. Subsequently, the postprandial GMA was recorded for two periods (2 h and 4 h), separated by a 15-min break. A typical flu-like syndrome was observed in 91.7% of patients in group A, and in 92.3% of patients in group B, thus providing evidence of the pharmacodynamic efficiency of the IFNA administration. In the fasted state, IFNA brought about a negligible increase in the rhythmicity and power of the gastric slow waves. IFNA did not elicit any statistically significant effect on gastric slow-wave activity postprandially. Acute administration of interferon does not involve any deterioration of GMA that could be linked to the previously reported upper abdominal symptoms in patients undergoing treatment with this drug.

Daily administration of interferon alpha 2b and utility of combination therapy with ribavirin as initial treatment for chronic hepatitis C: Follow up of patients

Daily administration of interferon alpha 2b and utility of combination therapy with ribavirin as initial treatment for chronic hepatitis C: Follow up of patients

Effect of interferon-alpha2b administration on rat liver regeneration after partial hepatectomy.

The purpose of the present study was to delineate the effect of interferon-alpha2b (IFN-alpha2b) administration on the liver regenerative capacity after partial hepatectomy in rats. The administration of IFN-alpha2b simultaneously with partial hepatectomy did not affect hepatic proliferation in a statistically significant manner. When IFN-alpha2b was administered either 2 or 12 hr postoperatively, an inhibition of hepatocyte proliferation was observed 24 hr postoperatively, while at further time intervals up to 48 hr, DNA synthesis remained similar to that observed in the simply partially hepatectomized rats. The enzyme thymidine kinase (TK), has been implicated in the suppression of proliferation in interferon-treated cell cultures. In all IFN-alpha2b-treated groups of rats, alterations of TK activity were observed without being correlated to the liver regenerative status. Additionally, the administration of the polyamine putrescine in partially hepatectomized rats treated at the time of surgery with IFN strongly enhanced TK activity, but did not affect DNA biosynthesis. In the above-mentioned in vivo model of controlled cellular proliferation, the administration of IFN-alpha2b affected the rate of hepatocyte proliferation depending on the time of its administration; this effect was not correlated to the enzymatic activity of TK, as inhibited TK activity is responsible for the suppressed DNA synthesis in in vitro systems.

Influence of Biological Response Modifiers

Human recombinant interferon-alpha-2b (IFN) is known to inhibit growth of both normal and tumor cells and to stimulate immune effector cell function. We have previously shown that IFN and other biological response modifiers augment accumulation of radiolabeled antibodies in tumors. This investigation demonstrates that 30 min post i.m. administration of IFN significantly (p < 0.01) enhances tumor perfusion in tumor-bearing mice and persists for a much longer time than in normal tissue, which, in part, may contribute to the enhanced tumor uptake of radiolabeled monoclonal antibodies within 1.5 h of their administration. Histological examinations of tumors obtained from animals receiving IFN 72 h previously did not show changes in inflammatory cells. Our investigation shows that laser Doppler flowmetry and color Doppler imaging can provide an excellent means of measuring tumor perfusion changes in small living animals where radioactive tracers cannot be used.

Erythropoietin beim multiplen Myelom

In a 59-year-old man with multiple myeloma (kappa-light chain paraproteinaemia) in stage IIIB, bone marrow infiltration with atypical plasma cells was reduced by five cytostatic treatment courses with vincristine, melphalan, cyclophosphamide and prednisone (VMCP protocol), but anaemia requiring blood transfusion persisted (haemoglobin concentration 5.3 g/dl). Even administration of interferon alpha-2b (5 million units s.c. every other day) failed to alter this. Only a combination of interferon and erythropoietin (150 U/kg i.v. every other day) achieved lasting regression of the anaemia (haemoglobin concentration up to 14 g/dl). In four other anaemic patients with multiple myeloma, stage III, treated according to the VMCP protocol but without additional interferon, erythropoietin did not improve erythropoiesis.