Is interferon-α a neuromodulator?

Dafny, Nachum

doi:10.1016/s0165-0173(97)00029-5

Cited by 55 publications

(34 citation statements)

References 132 publications

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“…Most neurotropic viruses reach the CNS by using either of the following three mechanisms - BBB crossing after viremia, Trojan horse mechanism or axonal transport. Type I and III IFNs are important to limit these early stages of viral infection; however, the basal activity of IFN appears to be low within the CNS [10]. The phosphoprotein of the highly neurotropic RV is a nonstructural protein known to interfere with various steps of IFN production, response and effector activity.…”

Section: Discussionmentioning

confidence: 99%

“…It is secreted by fibroblasts, T cells, macrophages, plasmacytoid monocytes, dendritic cells and natural killer cells, and therefore also came to be classified as the ‘leukocyte' IFN. IFN-α is considered a neuromodulator since it participates in many regulatory functions of the central nervous system (CNS) [10]. It has been the most successful antiviral therapy employed for the treatment of hepatitis C virus [11] and human immunodeficiency virus infection [12].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α

Mehta

Mukherjee

Balasubramanian

et al. 2014

Neuroimmunomodulation

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Objective: Recombinant human interferon (rhIFN)-α is a potent immunoregulator having a wide range of therapeutic applications. In the present study, rhIFN-α was evaluated for its neuroimmunomodulatory activity. Method: Dose-dependent gene expression of cytokines and chemokines in the brain of rhIFN-administered mice was studied using real-time SYBR green PCR. Results: Statistically significant increase in expression levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IFN-γ were observed. Conclusion: The findings indicate that rhIFN-α may be used at an optimized dose to cause appropriate neuromodulation of cytokine/chemokine secretion that can aid in the development of therapeutic approaches for many infectious diseases of the central nervous system for which therapies are lacking.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α

Mehta

Mukherjee

Balasubramanian

et al. 2014

Neuroimmunomodulation

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“…Various neurological side effects have been found associated with the therapeutic use of IFN, including impaired learning and memory (13), and type I IFNs interfere with hippocampal synaptic plasticity (14,38). In addition, STAT1-dependent signaling pathways have been shown to induce dendritic atrophy and perturb synaptogenesis and synaptic maturation in cultured hippocampus neurons (28,61).…”

Section: Discussionmentioning

confidence: 99%

Altered Central Nervous System Gene Expression Caused by Congenitally Acquired Persistent Infection with Lymphocytic Choriomeningitis Virus

Kunz

Rojek

Roberts

et al. 2006

J Virol

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Neonatal infection of most mouse strains with lymphocytic choriomeningitis virus (LCMV) leads to a life-long persistent infection characterized by high virus loads in the central nervous system (CNS) inInfection of the central nervous system (CNS) in humans by various DNA and RNA viruses can represent a severe health problem. Acute viral infections of the CNS frequently result in the destruction of specific neural cell populations as a direct consequence of virus multiplication or as a result of the host's antiviral immune response (23, 26). Many viruses, however, adopt a noncytolytic strategy of multiplication and can escape from the host immune surveillance by use of a plethora of mechanisms that may result in long-term persistent infections of the CNS. Despite the absence of overt signs of pathology such as cell lysis and inflammation, these infections can lead to severe alterations in neuronal function (45, 46) manifested by cognitive and behavioral impairment (20,30,39,60). This, in turn, has led to the hypothesis that viruses may contribute to a variety of CNS disorders whose etiologies remain unknown (40,44).The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) provides an important model system for the investigation of the mechanisms and consequences of viral persistence in the CNS (8,16,18,42,43). Furthermore, increasing evidence indicates that LCMV might be a neglected human pathogen of clinical significance (3,4,64). LCMV has a noncytolytic strategy of multiplication, which enables the virus to persist both in vivo and in cultured cells. Neonatal infection of mice with LCMV leads to the establishment of a life-long persistent infection (LCMV-Pi). Brains of LCMV-Pi mice contain high virus load primarily in neurons in the neocortex, limbic system, and certain hypothalamic regions (19,53). Neither inflammation nor cytolysis occurs within the brain parenchyma of LCMV-Pi mice. However, as adults LCMV-Pi mice exhibit an impaired learning ability and a reduced tendency to explore a novel environment (20,25). Since cognitive defects occur in the absence of overt signs of pathology, we hypothesized that chronic virus infection might contribute to neuronal dysfunction by altering the host's gene expression profile. Accordingly, previous studies have shown altered levels of acetylcholine enzymes (46) as well as neurotransmitter mRNAs (31) in LCMV-infected mice. Moreover, we have documented that LCMV persistence causes a specific reduction in expression of the growth-associated protein 43 (GAP-43), a well-established marker of neuroplasticity (5) in hippocampus (15). LCMV persistent infection reduced GAP-43 mRNA levels by affecting both the rate of GAP-43 transcription and the posttranscriptional stabilization of GAP-43 mRNA (10).In the present study, we aimed at the identification of additional host genes whose expression is changed in the CNS of mice persistently infected with LCMV. To recreate the natural route of congenital viral CNS infection (2), we established a

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“…IFN-α has been proven to have direct antiviral, antiproliferative and immunomodulatory properties [1]. There are also many reports demonstrating that IFN-α participates in important functions of the nerve system and suggesting that IFN-α is a neuromodulator [2,3,4,5]. Several studies suggested that IFN-α played an important role in nociception [6,7].…”

Section: Introductionmentioning

confidence: 99%

Interferon-Alpha Enhances Excitatory Transmission in Substantia Gelatinosa Neurons of Rat Spinal Cord

Qin¹,

Hou²,

Fang³

et al. 2012

Neuroimmunomodulation

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Objective: It has been shown that interferon-α (IFN-α) is synthesized and secreted by macrophages, monocytes, T lymphocytes, glial cells and neurons. IFN-α has been shown to have an antinociceptive effect at the supraspinal level in the nerve system. However, it is unclear how IFN-α is involved in the modulation of nociceptive transmission in the spinal cord. Methods: In the present study, IFN-α was used to test the potential functional roles in the nociceptive transmission. Using the whole-cell patch-clamp technique, we examined the effects of IFN-α on substantia gelatinosa (SG) neurons in the dorsal root-attached spinal cord slice prepared from adult rats. Results: We found that IFN-α increased glutamatergic excitatory postsynaptic currents evoked by the stimulation of either Aδ or C afferent fibers. Further studies showed that IFN-α treatment dose-dependently increased spontaneous excitatory postsynaptic current frequency in SG neurons, while not affecting the amplitude. Moreover, intrathecal antibody of IFN-α could reduce nociceptive responses in formalin test. Conclusions: These results suggest that IFN-α presynaptically facilitates the excitatory synaptic transmission to SG neurons. The nociceptive responses could be inhibited by IFN-α antibody in the formalin test. Thus, IFN-α enhances the nociceptive transmission, which contributes to the behavioral nociceptive responses.

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Is interferon-α a neuromodulator?

Cited by 55 publications

References 132 publications

Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α

Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α

Altered Central Nervous System Gene Expression Caused by Congenitally Acquired Persistent Infection with Lymphocytic Choriomeningitis Virus

Interferon-Alpha Enhances Excitatory Transmission in Substantia Gelatinosa Neurons of Rat Spinal Cord

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