[Characterization and comparison of interferon reference standards using UPLC-MS].

The study aims to characterize and compare interferon reference standards from 5 manufacturers. By testing molecular mass and trypsin-digested peptide mass mapping, the amino acid sequence was verified and post-translational modifications such as disulfide bond were identified. Results show that the molecular mass and amino acid sequence were consistent with theory; the disulfide bonds of 4 lots of interferon were Cys1-Cys98/Cys29-Cys138, 1 lot was Cys29-Cys139/Cys86-Cys99; N-terminal "+Met", acetyl N-terminal and Met oxidation were identified in part of the sample. UPLC-MS can be used to characterize and compare interferon reference standards from different manufacturers.

Interferón ß, microangiopatía trombótica y síndrome nefrótico / Interferon ß, nephrotic syndrome and thrombotic microangiopathy

No disponible

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.

BACKGROUND: Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and randomized trials and systematic reviews of treatment have been published. OBJECTIVES: The aim of this guideline was to prepare consensus guidelines on the definition, investigation, and treatment of CIDP. METHODS: Disease experts and a representative of patients considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements that were agreed in an iterative fashion. RECOMMENDATIONS: The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were as follows: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (good practice point); (3) if IVIg and corticosteroids are ineffective, plasma exchange should be considered (level A recommendation); (4) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (good practice point); and (5) symptomatic treatment and multidisciplinary management should be considered (good practice point).

Biological assays for interferons.

Interferons (IFN) are potent biologically active proteins synthesised and secreted by somatic cells of all mammalian species. They have been well characterised, especially those of human origin, with respect to structure, biological activities, and clinical therapeutic effects. While structural differences are known to exist among the IFN species that constitute the "IFN family" and despite the existence of different receptors for type I and type II IFN, all species have been shown to exert a similar spectrum of in vitro biological activities in responsive cells. Principal among the biological activities induced by IFN is antiviral activity, the activity used to originally define IFN. Antiviral activity of IFN is mediated via cell receptors and is dependent on the activation of signalling pathways, the expression of specific gene products, and the development of antiviral mechanisms. Sensitivity of cells to IFN-mediated antiviral activity is variable, and depends on a number of factors including cell type, expression of IFN receptors and downstream effector response elements, effectiveness of antiviral mechanisms, and the type of virus used to infect cells. Nevertheless, by the judicious use of sensitive cell lines in combination with appropriate cytopathic viruses, effective assays to measure the antiviral activity have been developed. Historically, "antiviral assays" (AVA) were the first type of biological assays that were developed to measure the relative activity or potency of IFN preparations. However, the subsequent discoveries of several other biological activities of IFN has opened the way to the development of assays based on one or other of these activities. The latter include inhibition of cell proliferation, regulation of functional cellular activities, regulation of cellular differentiation and immunomodulation. More recently, the cloning of IFN responsive genes has led to the development of "reporter gene assays". In this case, the promoter region of IFN responsive genes is linked with a heterologous reporter gene, for example, firefly luciferase or alkaline phosphatase, and transfected into an IFN-sensitive cell line. Stably transfected cell lines exposed to IFN increase expression of the reporter gene product in direct relation to the dose of IFN, the readout being a measure of this product's enzymic action. The current review aims to give a critical overview of the development, specificity, standardisation and present use of the various biological assay methods now available for the quantification of IFN activity.

Effective and safe interferon treatment for Japanese patients with chronic myelogenous leukemia relapse after bone marrow transplantation. The Nagoya Blood and Marrow Transplantation Group.

The purpose of this study was to assess the efficacy and safety of interferon (IFN) treatment in patients with a relapse of chronic myelogenous leukemia (CML) after bone marrow transplantation in Japan. Accordingly, we retrospectively analyzed the results obtained from 8 patients treated with IFN by the Nagoya Blood and Marrow Transplantation Group. One of 3 patients with hematologic relapse and all 5 patients with cytogenetic relapse achieved complete cytogenetic response (CCR). The median time to achieve CCR was 8 months (range, 3-16 months). One patient relapsed 9 months after starting IFN and died of blast crisis. CCR was maintained for a median duration of 47 months (range, 9-79 months) in the remaining 5 patients. The median duration of survival of these 5 patients after starting IFN was 58 months (range, 12-89 months). At the time of this report, 2 patients who did not attain CCR have survived for 81 months and 142 months after starting IFN, respectively. During IFN treatment, 1 patient showed a transient deterioration of chronic graft-versus-host disease, and no treatment-related deaths were observed. These results suggest that treatment with IFN for CML patients who relapse after bone marrow transplantation is effective and safe. A prospective study to compare IFN with donor lymphocyte infusion is necessary to establish the optimal strategy for the treatment of CML patients who relapse after bone marrow transplantation.

Interferon standardization and designations.

A large number of different human and nonhuman interferon (IFN) preparations are now available for either research purposes or commercial use. Consistency of results can be achieved only through rigorous application of biologic standards and individual species designation. International standards for the potency determinations of these preparations have been produced in accordance with World Health Organization (WHO) guidelines and are available for calibrating assays. Until recently, potency has been assessed purely as a measure of antiviral activity expressed in international units. Other biologic properties are now also being considered, including antiproliferation and immunomodulation. Indirect methods of measuring IFN, such as radioimmunoassay or enzyme immunoassay, if fully validated, may also provide useful estimates of function. Reference antisera are useful for characterizing IFN preparations and for monitoring neutralization assays for detecting anti-IFN antibodies but should not have a function in assay calibration. Factors to be considered when referring to specific designations for pure IFN species include distinctions for the species of origin, any mutant or hybrid forms, the method of production, and the presence of additional glycosylation.

[Effects of human interferons and 60cobalt radiation on canine and feline tumour cells-preclinical studies]. / Human-Interferon und 60Kobalt-Bestrahlung bei Tumorzellen des Hundes und der Katze--präklinische Studien.

This study examined the effects of recombinant human interferons (rHuIFN) alpha 2a, alpha 2b and gamma on canine and feline tumour-cell proliferation and radiosensitivity. Sensitivity of the cell lines to radiation and rHuIFN varied according to the histologic origin of the cells. In radiation experiments, one fraction of 400 cGy produced survival rates of between 76 and 25%. Sensitivity to IFN was higher in cell lines derived from round cell tumours compared to those derived from solid tumors. At doses of 100 and 1000 U/ml IFN alpha and IFN gamma, survival rates of between 70 and 80% were observed. In combined treatment experiments, increase in IFN or radiation dose produced higher cell kills. Increasing the number of fractions had the most pronounced effect. Even small doses of human interferons can have significant effects on animal tumour cells in vitro.

Human papillomavirus infection and therapy with interferon.

The studies summarized have shown that therapy of condylomata acuminata with interferon is effective. The route of administration does not appear to influence the results; the intralesional, intramuscular, and subcutaneous routes were effective. Additional research is required to determine whether the natural interferon or recombinant product is superior. The appropriate administration schedule may also not have been attained.

[Current state of national or international standards of interferons and cytokines].

Expert committee on Biological standardization (ECBS) of WHO had asked for an advisory committee for preparation of WHO international cytokine standards because of complexities by the rapid increase of number of cytokine molecules some of which are entered into clinical trials. The new meeting of the WHO informal Consultation on Cytokine standards was started from last spring and going to be held annually. The main mission of the committee was considered to be promoting the use of WHO international cytokine standards and reference materials etc., which must be available world wide. Various standard preparations of cytokines and growth factors are available at the National Institute of Biological Standards and Control (NIBSC) in the United Kingdom, some of which have been accepted by WHO as international standards (Table 1). Japanese national standards which had been prepared before establishment of WHO standards, and being labeled as Japanese reference Units (JRU) have to be calibrated with WHO standards to know International Units (IU). Japanese national references of IL-2 and TNF alpha were calibrated by collaboration with related companies and NIH Japan and the concluded results are obtained as follows. IL-2 (rec. DNA):1JRU = 1 IU TNF alpha (rec. DNA):1JRU = 35 IU

Thirty-ninth report / Thirty-ninth report

This report contains the deliberations and recommendations of an expert committee commissioned by the World Health Organization to coordinate activities leading to the establishment of international reference materials and the adoption of international requiremenst for the production and control of vaccines and other biologicals. The report starts with a discussion of general isues brought to the Committee's attention and provides information on the status and developemnt of international reference materials for various antibiotics, antibodies, antigens, blood producs, endocrinological substances, cytokines, allergens, and other biologicals. The second part of the report, of particular relevance to manufacturers and national control authorities, contains details of the WHO procedure for evaluating and acceptability of vaccines proposed to United Nations agencies for use in immunization programmes and three specific sets of requiremnts for hepatitis B vaccines made by recombinant DNA techniques, for human interferons prepared from lymphoblastoid cells, and the collection, processing, and quality control of blood, blood components, and plasma derivatives

Biological standardization of cytokines.

Cytokines are a heterogenous group of biologically active proteinaceous molecules which regulate cell growth, differentiation and function. They are secreted, soluble (non-antibody) mediators which are active in very small quantities and thus may be considered to be a subset of hormones. Many cytokines, especially those affecting the immune system, are being evaluated in the clinic, mainly in the area of cancer therapy. Cytokines constitute a group of proteins which cannot be completely characterized by chemical and physical features alone. Since they are highly biologically active and generally have wide-ranging pharmacological effects, they must necessarily be characterized from a biological standpoint. For convenience, the biological properties of cytokines are assessed in responsive in vitro cell systems. The development of specific biological assays to measure cytokine activities has rapidly progressed in the last decade and has led to attempts to standardize these activities. Standardization of interferons in terms of antiviral activity, for example, has been largely successful in establishing a common international unitage for interferon activity. The latter was dependent on the development and establishment of WHO international interferon reference preparations or standards. Standardization of other cytokines including interleukin-1, interleukin-2 and tumour necrosis factor is currently underway and interim reference preparations have been made available. It is likely that there will be a growing requirement for biological standardization of colony stimulating factors and other growth and differentiation factors.