Impending anterior ischemic optic neuropathy with elements of retinal vein occlusion in a patient on interferon for polycythemia vera.

We describe the course and likely pathophysiology of impending anterior ischemic optic neuropathy (AION) and retinal vein occlusion in a 56-year-old man with polycythemia vera managed with interferon alpha for 2 years. Our patient presented with decreased vision, scintillating scotomata, and floaters. Fundus examination findings and results of a fluorescein angiogram led to the diagnosis of impending AION and retinal vein occlusion. Considering that both polycythemia vera and interferon have possible influences on vascular occlusion and optic disc edema, we stopped interferon treatment and immediately attempted to treat the polycythemia vera empirically with pentoxifylline and any interferon-associated inflammation with prednisone. Our patient experienced complete resolution of fundus abnormalities and return of normal vision within 3 weeks, which may be attributed to our successful treatment of both etiologies. Thus, further study is warranted to elucidate the treatment of both polycythemia vera and interferon-induced impending AION

Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy.

A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing–remitting multiple sclerosis patients, aged 18–50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 mg (three times weekly) for 12 months, were randomized to combination therapy (interferon+atorvastatin 20mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A (n 1⁄4 21) or B (n 1⁄4 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline (p 1⁄4 0.007) and significantly fewer relapses versus the two pre-randomization years (p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p 1⁄4 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone

Alpha/beta and gamma interferons are induced by infection with noncytopathic bovine viral diarrhea virus in vivo

In contrast to the results of previous in vitro studies, experimental infection of calves with noncytopathic bovine viral diarrhea virus (ncpBVDV) was found to induce strong alpha/beta and gamma interferon responses in gnotobiotic animals. These responses were associated with depressed levels of transforming growth factor β (TGF-β) in serum. The results of this study indicate that the immunosuppression caused by ncpBVDV is not associated with low interferon responses or elevated levels of TGF-β

Multiple tumor suppressors regulate a HIF-dependent negative feedback loop via ISGF3 in human clear cell renal cancer.

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft model as its loss significantly enhances tumor growth. Conversely, reactivation of ISGF3 retards tumor growth by PBRM1-deficient ccRCC cells. Thus after VHL inactivation, HIF induces ISGF3, which is reversed by the loss of secondary tumor suppressors, suggesting that this is a key negative feedback loop in ccRCC. © 2018, Liao et al

Gamma interferon-dependent clearance of cytomegalovirus infection in salivary glands

Cytomegalovirus (CMV), similar to other members of the Herpesviridae family, can establish both persistent and latent infections. Each of the CMVs that are found in many animal species replicates in the salivary gland, and oral secretion represents a source of horizontal transmission. Locally restricted replication characterizes the immunocompetent individual, whereas in the immunocompromised host, protean disease manifestations occur due to virus dissemination. The virus is cleared by immune surveillance, and CD8+ T lymphocytes play a major role. Remarkably, certain cell types of salivary gland tissues are exempt from CD8+ T-lymphocyte control of murine CMV infection and require the activity of CD4+ T lymphocytes. The results presented here suggest that this activity is a function of Th1 cells. Neutralization of endogenous gamma interferon abrogated the antiviral activity of Th1 cells but not that of CD8+ T lymphocytes in other tissues. Neutralization of endogenous gamma interferon did not interfere with the induction of the cellular and humoral immune response but acted during the effector phase. Recombinant gamma interferon could not replace the function of Th1 cells in vivo and had limited direct antiviral activity in vitro. The results therefore suggest that gamma interferon represents one, but not the only, essential factor involved in salivary gland clearance, establishment of CMV latency, and, eventually, the control of horizontal transmission

Regulation of Murine Class I Genes by Interferons is Controlled by Regions Located Both 5' and 3' to the Transcription Initiation Site

Interferons regulate the expression of a large number of mammalian genes, including the major histocompatibility antigen genes. To investigate the mechanisms involved in interferon action, we have analyzed the ability of murine H-2Ld and H-2Dd DNA sequences to control the responses to interferon. The results indicate that interferon regulation of class I gene expression is complex and involves at least two mechanisms that are dependent on class I sequences located upstream and downstream to the transcription initiation site. In transfected mouse L cells, both of these regions are required for full enhancement of class I gene expression, with the major portion of the response controlled by the sequences located 3' to the transcription initiation site. The fine-mapping analysis of the 5' region-encoded response also suggests that recombinant alpha and gamma interferons may exert their effects on class I gene expression by using different cis-acting regulatory sequences

‘It’s been a long haul, a big haul, but we’ve made it’: hepatitis C virus treatment in post-transplant patients with virus recurrence: An interpretative phenomenological analysis

The lived experience of both interferon-based and new interferon-free treatments in patients with hepatitis C virus remains understudied. To explore their journey through hepatitis C virus treatment, we interviewed seven post-transplant patients with recurrent hepatitis C virus. Three themes were identified using interpretative phenomenological analysis. Participants reported an ongoing sense of ontological uncertainty characterized by lack of control over their condition and treatment. Furthermore, an apposition of scepticism and hope accompanying each stage of hepatitis C virus treatment was described. A staged approach to psychological intervention tailored to the needs of the patient and their associated ‘stage’ of hepatitis C virus treatment was recommended

Interleukin -2 ( Il-2 ) and Gamma Interferon ( Ifn ? ) of Lymphocyte Culture Supernatant in Iron Deficiency Anemia Patients with Infection

Iron is an essential nutrient for every living cells because of it role as molecule fortransport of oxygen, as well as DNA synthesis through synthesis of ribonucleotidereductase. Iron deficiency anemia patients, especially pregnant women and children aremore susceptible to infection because of deterioration of their immune response. This wassupported by findings of decreased in phagocytic activities of white blood cells and Tcelllymphocyte proliferation impairment. Iron deficiency anemia (IDA) patients alsoaffect working capacities hence diminishing working outcomes. Although the underlyingmechanism of immune defect in iron deficiency anemia is not clearly understood,multifactor events considered play their contributing roles such as abnormality ofribonucleotide reductase enzym, impairment of T-cell proliferation and activities, alteredcytokine production of IL-2 and IFN?.The study was done to asses the relationship of IL-2 and gamma IFN withinfection in IDA patients on lymphocyte culture supernatant of IDA patients. Study wasconducted on cross-sectional analytic design. Sixty-four iron deficiency anemia patientstreated in Sanglah General Teaching Hospital were recruited, and 31 (48.4%) out of 64IDA patients were man and 33 (51.6%) women, have been selected for the study. Thisstudy found 17 (26.7%) IDA patients with infection, aged 38 ± 14.48 years and 47(73.3%) IDA patients without infection, with age average of 40.5 ± 14.4 years. Allvariables of data characteristics examined did not indicate any statistical significantdifference between group of IDA patients with infection and those without infection. Theaverage level of hemoglobin between the two groups did not differ statistically. Similarresult was obtained if samples were differentiated into severe (Hb&lt; 7g/dl) and mildanemia. The study also revealed that there were no differences of cytokine level observedbetween older and younger age (upper and below 44.5 years) in IDA patients withinfection and without infection. Furthermore, no differences of cytokine level were foundbased on gender between IDA male 10.9 (8.60 – 12,65) (pg/l) patients and IDA femalepatients 10.6 (7.50 – 13.43) (pg/l) with Z -0.490, p =0.624. Nevertheless, significantdifferences were noted between supernatant of IL-2 and IFN? in IDA patients withinfection when compared to IDA patients without infection (Z= - 2.509, p= 0.012 forsupernatant IL-2; and Z= -2.569, p= 0.010 for supernatant IFN?).The study conclusion is that level of IL-2 and IFN? from lymphocyte culturesupernatant of patient suffered from IDA with infection is significantly lower whencompared to IDA patient without infection. It therefore summarized that lower level ofIL-2 and gamma IFN in patients suffered from iron deficiency impaired their immune response to certain infections therefore this findings support the theory that IDA patientsmore susceptible to get infected

Synthesis of IFN-β by Virus-Infected Chicken Embryo Cells Demonstrated with Specific Antisera and a New Bioassay

Transcripts of interferon-α(IFN-α) and IFN-β genes are present in virus-infected chicken cells, but because of a lack of appropriate assays and reagents, it was unclear if biologically active IFN-β is secreted. We have established a nonviral bioassay for the sensitive detection of chicken IFN (ChIFN). This assay is based on a quail cell line that carries a luciferase gene that is controlled by the IFN-responsive chicken Mx promoter. Luciferase activity was strongly stimulated when the indicator cells were incubated with ChIFN-α, ChIFN-β, or ChIFN-γ but not with chicken interleukin-1β (ChIL-1β). Unlike the classic antiviral assay that preferentially detects ChIFN-α, the Mx-luciferase assay detected ChIFN-α and ChIFN-β with similar sensitivity. With the help of this novel assay and with rabbit antisera specific for either IFN-α or IFN-β, we analyzed the composition of IFN in supernatants of virus-infected chicken embryo cells. Virtually all IFN produced in response to Newcastle disease virus (NDV) was IFN-α. However, IFN produced in response to influenza A or vaccinia virus (VV) was a mixture of usually more than 80% IFN-α and up to 20% IFN-β. Thus, IFN-α and IFN-β both contribute to the cytokine activity in supernatants of virus-infected chicken cells. Furthermore, the infecting virus appears to determine the IFN subtype composition