Journal of Interferon ResearchVol. 14, No. 5 Interleukin-6 Antibodies in Rheumatoid ArthritisJ. WIJDENES, E. RACADOT, and D. WENDLINGJ. WIJDENESSearch for more papers by this author, E. RACADOTSearch for more papers by this author, and D. WENDLINGSearch for more papers by this authorPublished Online:5 May 2009https://doi.org/10.1089/jir.1994.14.297AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Interleukin-6 Antibodies in Rheumatoid Arthritis." , 14(5), pp. 297–298FiguresReferencesRelatedDetailsCited byAlterations in Cytokine Profile and Dendritic Cells Subsets in Peripheral Blood of Rheumatoid Arthritis Patients before and after Biologic Therapy1 September 2009 | Annals of the New York Academy of Sciences, Vol. 1173, No. 1Effect of interleukin-6 blockade on tissue factor-induced coagulation in human endotoxemiaCritical Care Medicine, Vol. 32, No. 5Tumor Necrosis Factor-α Blockade: A Novel Therapy for Rheumatic DiseaseClinical Immunology, Vol. 103, No. 3Anti-TNFα Therapy of Rheumatoid Arthritis: What Have We Learned?Annual Review of Immunology, Vol. 19, No. 1Role of pro-inflammatory cytokines in rheumatoid arthritisSpringer Seminars in Immunopathology, Vol. 20, No. 1-2ROLE OF CYTOKINES IN RHEUMATOID ARTHRITISAnnual Review of Immunology, Vol. 14, No. 1Effects of antirheumatic agents on cytokinesSeminars in Arthritis and Rheumatism, Vol. 25, No. 4 Volume 14Issue 5Oct 1994 To cite this article:J. WIJDENES, E. RACADOT, and D. WENDLING.Interleukin-6 Antibodies in Rheumatoid Arthritis.Journal of Interferon Research.Oct 1994.297-298.http://doi.org/10.1089/jir.1994.14.297Published in Volume: 14 Issue 5: May 5, 2009PDF download
The expression of mRNAs encoding interferons (IFNs) and IFN-inducible proteins has been studied in psoriatic lesions and in noninvolved skin. The specific mRNAs have been detected by in situ hybridization using antisense RNAs. Signals for the expression of IFN-gamma mRNA have been found exclusively in cells of psoriatic lesions, and most likely represent a subpopulation of infiltrating leukocytes. Weak signals of IFN-alpha mRNA have been detected throughout the hyperkeratotic epidermis, although specific signals for IFN-beta mRNA expression were not detectable. The expression of two IFN-alpha-inducible gene products, namely the MxA protein and the 2'-5' oligoadenylate (2-5A) synthetase, have been studied as markers for the local activation of the IFN-alpha system. Expression of MxA mRNA and protein was observed in psoriatic keratinocytes, but not in normal appearing keratinocytes adjacent to the lesions. Similarly, 2-5A synthetase expression was markedly elevated in psoriatic keratinocytes. The results of the present study indicate that the IFN-alpha system is selectively activated in psoriatic lesions, although it remains silent in noninvolved skin. The implications of this finding are discussed within the boundaries of current understanding of the cytokine network.
The in vivo interferon (IFN) activation in Crohn's disease was evaluated by measuring the relative amounts of IFN-alpha and -gamma mRNA in freshly isolated human lamina propria mononuclear cells (LPMC) from patients with Crohn's disease and controls. Both IFN-gamma and IFN-alpha mRNA, as estimated by dot blot analysis, were increased in Crohn's disease (LPMC), although the relative amounts of IFN mRNA appeared to differ among patients. Appreciable amounts of IFN-gamma mRNA were found in Crohn's disease peripheral blood mononuclear cells (PBMC) extracts, whereas the same cells were negative for IFN-alpha mRNA. Only minute amounts of IFN-gamma RNA were found sporadically in control LPMC while no IFN-alpha was detected. Control PBMC were shown to be virtually negative for both IFN-alpha and IFN-gamma mRNA. These data suggest that IFN induction in the normal human gut is a well-controlled function and that in Crohn's disease tissues, both IFN-gamma and IFN-alpha production are dysregulated. The increased IFN activity may represent a major feature in the induction and perpetuation of the chronic inflammatory process in Crohn's disease.
Anion superoxide (O-2(-)) production and glucose metabolism was studied in murine macrophages following in vivo or in vitro treatment with human recombinant interferon-alpha 2b (IFN-alpha 2b). The PMA-dependent O-2(-) production was inhibited by IFN-alpha 2b in a concentration- and time-dependent manner. NO2- production by macrophages in culture was slightly inhibited (about 16%) at 30 nM IFN-alpha and a clear decrease (35%) was obtained with 150 nM IFN-alpha. Low doses (0.3 and 3 nM IFN-alpha) had no effect. Also, IFN alpha 2b inhibited lactate release and (H2O)-H-3 production from [2-H-3] and [3-H-3]glucose in macrophages isolated after in vivo treatment for 24 h. The data support an inhibitory role of IFN-alpha in the metabolic activation of macrophages and suggest a putative mechanism for the inhibition of some macrophage functions as previously reported.
Journal of Interferon ResearchVol. 14, No. 4 Naturally Occurring Autoantibodies to Interleukin-1α, Interleukin-6, Interleukin-10, and Interferon-αKLAUS BENDTZEN, MORTEN B. HANSEN, MARCUS DIAMANT, CHRISTIAN ROSS, and MORTEN SVENSONKLAUS BENDTZENSearch for more papers by this author, MORTEN B. HANSENSearch for more papers by this author, MARCUS DIAMANTSearch for more papers by this author, CHRISTIAN ROSSSearch for more papers by this author, and MORTEN SVENSONSearch for more papers by this authorPublished Online:5 May 2009https://doi.org/10.1089/jir.1994.14.157AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Naturally Occurring Autoantibodies to Interleukin-1α, Interleukin-6, Interleukin-10, and Interferon-α." , 14(4), pp. 157–158FiguresReferencesRelatedDetailsCited byThe level of natural autoantibodies to IFN-gamma in varicella infection treated with antiviral drug Anaferon for children: A pilot studyImmunology Letters, Vol. 222Enhanced Immunogenicity of HIV-1 Envelope gp140 Proteins Fused to APRIL23 September 2014 | PLoS ONE, Vol. 9, No. 9Autoantibodies Induced by Chimeric Cytokine-HIV Envelope Glycoprotein Immunogens15 May 2014 | The Journal of Immunology, Vol. 192, No. 10Cytokines as Biomarkers in Rheumatoid ArthritisMediators of Inflammation, Vol. 2014Immunoregulation by Naturally Occurring and Disease-Associated AutoantibodiesTransfusion-related inhibition of cytokines (TRICK). Experimental transfer of neutralizing autoantibodies to interleukin-6 by plasma transfusionsVox Sanguinis, Vol. 92, No. 3Identification of natural antibodies to interleukin-18 in the sera of normal humans and three nonhuman primate speciesClinical Immunology, Vol. 109, No. 2Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential1 March 2003 | Pharmacological Reviews, Vol. 55, No. 1Natural And Induced Anticytokine Antibodies In Humans1 December 2009Antibodies Binding Granulocyte–Macrophage Colony Stimulating Factor Produced by Cord Blood-Derived B Cell Lines Immortalized by Epstein–Barr Virus in VitroCellular Immunology, Vol. 204, No. 2Natural and therapeutically-induced antibodies to cytokinesBiotherapy, Vol. 10, No. 4The Biology of Interferon-α and the Clinical Significance of Anti-Interferon Antibodies1 July 2009 | Leukemia & Lymphoma, Vol. 29, No. 3-4Naturally occurring and therapy-induced antibodies to human granulocyte colony-stimulating factor (G-CSF) in human serumJournal of Cellular Physiology, Vol. 173, No. 2Anti-cytokine autoantibodies: Epiphenomenon or critical modulators of cytokine actionBiotherapy, Vol. 10, No. 1Natural and Therapy-Induced Anti-GM-CSF and Anti-G-CSF Antibodies in Human Serum1 July 2009 | Leukemia & Lymphoma, Vol. 26, No. sup1Anti-cytokine autoantibodies: Epiphenomenon or critical modulators of cytokine actionBiological effects of the interferons and other cytokinesBiotherapy, Vol. 8, No. 3-4Biological effects of the interferons and other cytokinesCytokine AutoantibodiesHuman leukocyte interferon alpha: Structure, pharmacology, and therapeutic applicationsMedicinal Research Reviews, Vol. 15, No. 5Cytokines and autoantibodies to cytokines23 December 2008 | STEM CELLS, Vol. 13, No. 3 Volume 14Issue 4Aug 1994 To cite this article:KLAUS BENDTZEN, MORTEN B. HANSEN, MARCUS DIAMANT, CHRISTIAN ROSS, and MORTEN SVENSON.Naturally Occurring Autoantibodies to Interleukin-1α, Interleukin-6, Interleukin-10, and Interferon-α.Journal of Interferon Research.Aug 1994.157-158.http://doi.org/10.1089/jir.1994.14.157Published in Volume: 14 Issue 4: May 5, 2009PDF download
Journal of Interferon ResearchVol. 14, No. 4 Specific Autoantibodies Directed Against Interferon-α in Pharmaceutically Prepared Human Immunoglobulin PreparationsC. ROSS, M. SVENSON, M.B. HANSEN, G.L. VEIJLSGAARD, and K. BENDTZENC. ROSSSearch for more papers by this author, M. SVENSONSearch for more papers by this author, M.B. HANSENSearch for more papers by this author, G.L. VEIJLSGAARDSearch for more papers by this author, and K. BENDTZENSearch for more papers by this authorPublished Online:5 May 2009https://doi.org/10.1089/jir.1994.14.159AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Specific Autoantibodies Directed Against Interferon-α in Pharmaceutically Prepared Human Immunoglobulin Preparations." , 14(4), pp. 159–160FiguresReferencesRelatedDetailsCited ByAnticorps anti-cytokines : quel impact clinique en pathologie humaine ?La Revue de Médecine Interne, Vol. 43, No. 9The level of natural autoantibodies to IFN-gamma in varicella infection treated with antiviral drug Anaferon for children: A pilot studyImmunology Letters, Vol. 222A rapid, accurate and robust particle-based assay for the simultaneous screening of plasma samples for the presence of five different anti-cytokine autoantibodiesJournal of Immunological Methods, Vol. 425Transfusion-related inhibition of cytokines (TRICK). Experimental transfer of neutralizing autoantibodies to interleukin-6 by plasma transfusionsVox Sanguinis, Vol. 92, No. 3High dose intravenous immunoglobulin treatment: Mechanisms of action1 January 2005 | Liver Transplantation, Vol. 11, No. 12IVIG - mechanisms of actionAllergy, Vol. 58, No. 7Natural and therapeutically-induced antibodies to cytokinesBiotherapy, Vol. 10, No. 4Anti-cytokine autoantibodies: Epiphenomenon or critical modulators of cytokine actionBiotherapy, Vol. 10, No. 1Anti-cytokine autoantibodies: Epiphenomenon or critical modulators of cytokine actionBiological effects of the interferons and other cytokinesBiotherapy, Vol. 8, No. 3-4Biological effects of the interferons and other cytokinesHuman leukocyte interferon alpha: Structure, pharmacology, and therapeutic applicationsMedicinal Research Reviews, Vol. 15, No. 5Cytokines and autoantibodies to cytokines23 December 2008 | STEM CELLS, Vol. 13, No. 3 Volume 14Issue 4Aug 1994 To cite this article:C. ROSS, M. SVENSON, M.B. HANSEN, G.L. VEIJLSGAARD, and K. BENDTZEN.Specific Autoantibodies Directed Against Interferon-α in Pharmaceutically Prepared Human Immunoglobulin Preparations.Journal of Interferon Research.Aug 1994.159-160.http://doi.org/10.1089/jir.1994.14.159Published in Volume: 14 Issue 4: May 5, 2009PDF download
In humans with advanced human immunodeficiency virus (HIV) infection, an interferon-alpha (IFN-alpha) response by a specialized blood mononuclear cell to herpes simplex virus (HSV) in vitro is associated with resistance to opportunistic infections. A cell type of unknown lineage, designated the natural IFN-producing cell (NIPC), has been identified preliminarily as the source of these IFNs and may have a role in other host defense functions. Earlier studies suggested the existence of analogous HSV-responsive cell populations in mice. The role specifically of IFN-alpha in the murine system, however, has not been characterized. Using IFN bioassay and neutralization with antisera against Type I IFNs and IFN-beta, we have defined the types and sources of IFNs produced by mice in response to in vivo and in vitro challenge with UV-inactivated HSV. After intraperitoneal inoculation with HSV, BALB/c and C57Bl/6 strains produced characteristically different levels of serum IFNs that appeared principally to be IFN-alpha. The response of mononuclear cells from these mice differed from that of the intact mouse. Isolated cells from bone marrow and spleen released detectable IFNs much later than did whole animals, and the IFNs produced by marrow, spleen, and peritoneal cells were usually neutralized by the anti-IFN-beta. Only bone marrow cells produced detectable amounts of IFN-alpha. Both intact mice and their cells became refractory to restimulation with similar kinetics.
A computer-built, three-dimensional, atomic-level model for human interferon-alpha (IFN-alpha) was constructed. This model was prepared using the primary amino acid sequence of consensus IFN-alpha (IFN-alpha Con1) and the alpha-carbon Cartesian coordinates of murine IFN-beta as a homolog guide to the model building. In agreement with an earlier report from this laboratory, the two domains 29-35 and 123-140 are in close spatial proximity in this model, and may constitute a receptor recognition domain, whereas the region bounded by residues 78-95 is somewhat removed from this region on the molecule and may constitute an alternative active site. Extrapolating from the model, we propose that, of the stretch 123-140, the residues that are exposed are 123, 125, 126, 128-130, and 132-139; and of the stretch 29-35, all are accessible. Additionally, we propose that there may be sufficient complexity in the Type 1 IFN receptor to account for the differential sensitivities between IFN-alpha s and IFN-beta that may be associated with residue differences in the region 78-95, specifically at residues 84, 86, and 87. This model conforms with experimental data that identify specific amino acid residues in human IFN-alpha that either do, or do not, affect the active conformation and biological activities of the molecule.
Journal of Interferon ResearchVol. 13, No. 3 Nomenclature of the Human Interferon GenesaPublished Online:5 May 2009https://doi.org/10.1089/jir.1993.13.243AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail "Nomenclature of the Human Interferon Genesa." , 13(3), pp. 243–244FiguresReferencesRelatedDetailsCited byAntimicrobial preservatives induce aggregation of interferon alpha-2a: The order in which preservatives induce protein aggregation is independent of the proteinInternational Journal of Pharmaceutics, Vol. 472, No. 1-2High yield soluble bacterial expression and streamlined purification of recombinant human interferon α-2aProtein Expression and Purification, Vol. 99Growth inhibitory effects of interferon‐α subtypes vary according to human liver cancer cell lines18 September 2006 | Journal of Gastroenterology and Hepatology, Vol. 21, No. 11EFFECTS OF INTERFERON-ALPHA SUBTYPES ON THE TH1/TH2 BALANCE IN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM PATIENTS WITH HEPATITIS VIRUS INFECTION–ASSOCIATED LIVER DISORDERSIn Vitro Cellular & Developmental Biology - Animal, Vol. 41, No. 1Activity of Hybrid Type I Interferons in Cells Lacking Tyk2: A Common Region of IFN-α 8 Induces a Response, but IFN-α2/8 Hybrids Can Behave Like IFN-β Dimitris Platis and Graham R. Foster7 July 2004 | Journal of Interferon & Cytokine Research, Vol. 23, No. 11High yield expression, refolding, and characterization of recombinant interferon α2/α8 hybrids in Escherichia coliProtein Expression and Purification, Vol. 31, No. 2The Relationship between Simian Immunodeficiency Virus RNA Levels and the mRNA Levels of Alpha/Beta Interferons (IFN-α/β) and IFN-α/β-Inducible Mx in Lymphoid Tissues of Rhesus Macaques during Acute and Chronic InfectionJournal of Virology, Vol. 76, No. 16Signaling through the JAK/STAT pathway, recent advances and future challengesGene, Vol. 285, No. 1-2HOW CELLS RESPOND TO INTERFERONSAnnual Review of Biochemistry, Vol. 67, No. 1Different Relative Activities of Human Cell-Derived Interferon-α Subtypes: IFN-α8 Has Very High Antiviral Potency G.R. FOSTER, O. RODRIGUES, F. GHOUZE, E. SCHULTE-FROHLINDE, D. TESTA, M.J. LIAO, G.R. STARK, L. LEADBEATER, and H.C. THOMAS28 March 2009 | Journal of Interferon & Cytokine Research, Vol. 16, No. 12Why Do So Many Cancer Patients Fail to Respond to Interferon Therapy? STEFAN EINHORN and DAN GRANDÉR28 March 2009 | Journal of Interferon & Cytokine Research, Vol. 16, No. 4Analysis of Human Interferon-α Gene Promoters by Multiple Sequence Alignment JOHN L. HOULE and NICOLA SANTORO28 March 2009 | Journal of Interferon & Cytokine Research, Vol. 16, No. 2Production and action of interferons: New insights into molecular mechanisms of gene regulation and expressionStructural elements required for receptor recognition of human interferon-gammaPharmacology & Therapeutics, Vol. 64, No. 1 Volume 13Issue 3Jun 1993 To cite this article:Nomenclature of the Human Interferon Genesa.Journal of Interferon Research.Jun 1993.243-244.http://doi.org/10.1089/jir.1993.13.243Published in Volume: 13 Issue 3: May 5, 2009PDF download
Journal of Interferon ResearchVol. 14, No. 4 Standardization of Cytokines and Their LigandsS.E. GROSSBERG and J.L. TAYLORS.E. GROSSBERG and J.L. TAYLORPublished Online:5 May 2009https://doi.org/10.1089/jir.1994.14.169AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byThe expression of potency of neutralizing antibodies for interferons and other cytokinesBiotherapy, Vol. 10, No. 1The Expression of Potency of Neutralizing Antibodies for Interferons and other Cytokines Volume 14Issue 4Aug 1994 To cite this article:S.E. GROSSBERG and J.L. TAYLOR.Standardization of Cytokines and Their Ligands.Journal of Interferon Research.Aug 1994.169-171.http://doi.org/10.1089/jir.1994.14.169Published in Volume: 14 Issue 4: May 5, 2009PDF download
Journal of Interferon ResearchVol. 14, No. 4 Natural IgG Autoantibodies in the Sera of Healthy IndividualsMICHEL D. KAZATCHKINEMICHEL D. KAZATCHKINESearch for more papers by this authorPublished Online:5 May 2009https://doi.org/10.1089/jir.1994.14.165AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byComparative Analysis of Antigen Specificities in the Monomeric and Dimeric Fractions of Intravenous ImmunoglobulinAnnals of the New York Academy of Sciences, Vol. 1051, No. 1Towards a better understanding of heterophile (and the like) antibody interference with modern immunoassaysClinica Chimica Acta, Vol. 325, No. 1-2Natural And Induced Anticytokine Antibodies In Humans1 December 2009Natural and therapeutically-induced antibodies to cytokinesBiotherapy, Vol. 10, No. 4 Volume 14Issue 4Aug 1994 To cite this article:MICHEL D. KAZATCHKINE.Natural IgG Autoantibodies in the Sera of Healthy Individuals.Journal of Interferon Research.Aug 1994.165-168.http://doi.org/10.1089/jir.1994.14.165Published in Volume: 14 Issue 4: May 5, 2009PDF download
Interferon (IFN) treatment of cells results in the induction of 2-5A-synthetases, double-stranded RNA-activated enzymes that produce unusual 5'-phosphorylated 2',5'-linked oligoadenylates known as 2-5A. 2.5A activates a unique IFN-induced endoribonuclease, the 2-5A-dependent RNase (RNase L), that is capable of degrading both viral and cellular RNA. The expression cloning of 2-5A-dependent RNase is leading to meaningful analysis of the physiological functions of the 2-5A system. For example, expression in mouse cells of a dominant-negative mutant form of 2-5A-dependent RNase suppressed both the antiencephalomyocarditis virus and anticellular activities of IFN. Future investigations into this intriguing ribonuclease pathway promise to provide an intricate view into a molecular pathway of IFN action.
Interferons alpha, beta, and gamma have been shown to exert systemic effects following their oral administration to mice. It was of importance to determine whether oral administration of another biologic response modifier, interleukin-2 (IL-2), could also exert systemic effects in mice. Two systemic effects, peripheral WBC suppression and bone marrow suppression, were evaluated. Oral administration of IL-2 was found to suppress the peripheral WBC count in a dose-dependent manner. Oral administration of IL-2 was also found to suppress the bone marrow proliferative activity. The levels of suppression of both peripheral WBC and myelopoietic progenitor cell numbers observed with orally administered IL-2 were comparable to those seen with subcutaneously administered IL-2. The results demonstrate that orally administered IL-2 can exert systemic effects. Further, the results raise the possibility that oral administration of IL-2 may have therapeutic potential.
A gene encoding chicken interferon (ChIFN) was cloned from a cDNA library made from primary chick embryo cells that had been ''aged'' in vitro so as to produce copious amounts of IFN upon induction. The coding region is predicted to produce a signal peptide of 31 amino acids and a mature protein of 162 amino acids with a molecular weight of 18,957. There are four potential N-glycosylation sites and six cysteine residues. Three disulfide bonds are possible, with two being common to most mammalian type I IFNs. A motif of 10 amino acids surrounding Cys-137 is highly conserved: It shows 80% homology with mammalian type I IFNs, but only 30% with a reported fish IFN. The T-rich 3' UTR displays the canonical element AATAAA required for polyadenylation, and contains six repeats of the octamer CTATTTAT that may be involved in down-regulating translation. Northern blots demonstrate that the accumulation of ChIFN mRNA correlates with induction of ChIFN determined by bioassay. Biologically active protein was synthesized in transfected mouse L cells using mRNA prepared in vitro from the cloned sequence. This activity was neutralized by a monoclonal antibody prepared against purified ChIFN. The ChIFN gene shows sequence identity at the amino acid/nucleotide level with consensus mammalian IFNs as follows: alpha (24/23%), beta (20/24%), omega (23/43%), tau (20/43%), gamma (3/31%), and with flatfish IFN (16/35%). The conserved features of the predicted ChIFN protein and the general similarity of predicted secondary structure suggest a molecule that fits the five alpha-helix three-dimensional topology reported for type I mammalian IFNs. The ChIFN gene appears to have shared a common ancestry with type P mammalian IFN genes at the time of the avian and mammalian divergence about 350 million years ago, but both differ significantly from a sequence reported to code for a flatfish IFN.
