Interleukin-1 and interleukin-2 production by peripheral blood mononuclear cells in multiple sclerosis patients

Selmaj, Krzysztof; Nowak, Zofia; Tchórzewski, H

doi:10.1016/0022-510x(88)90036-6

Cited by 26 publications

(11 citation statements)

References 31 publications

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“…This was first studied in unfractionated serum and CSF, and then in a number of samples after fractionation to evaluate eventual differences. These findings are in agreement with those of Selrnaj et al [25], who found no significant difference in IL-1 production by peripheral blood monunuclear cells in MS, OND or normal controls and a lower IL-2 production in MS patients in relapse. In our ease, the CSF was not concentrated but even after fractionation, there was no significant increase in activity.…”

Section: Discussionsupporting

confidence: 93%

Lymphocyte activating factor activity in the serum and cerebrospinal fluid of patients with multiple sclerosis

et al. 1990

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Serum and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS), patients with other (non-inflammatory) neurological diseases (OND), patients with non-inflammatory non-neurological diseases, and normal controls were assayed for lymphocyte activating factor (LAF) activity by thymocyte costimulation. LAF activity was detected in normal control sera, which did not differ significantly in this respect from MS or OND patient sera. Not were there significant differences by stage of MS (chronic progressive MS, MS in relapse and MS in remission) or between MS patients and the non-inflammatory non-neurological controls. Almost all the CFSs assayed presented lower values than did the corresponding sera. Serum and CSF after fractionation showed no significant increase in LAF activity except in the 2 MS patients in remission. From these data it may be assumed that LAF activity does not necessarily correspond to the clinical phase of MS. The possible role of LAF activity as a marker of MS progression has yet to be determined.

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Section: Discussionsupporting

confidence: 93%

Lymphocyte activating factor activity in the serum and cerebrospinal fluid of patients with multiple sclerosis

et al. 1990

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“…In addition the levels of soluble IL-2 receptor (sIL-2R) also appear to be elevated in the sera of patients with MS8,10–13 and in the CSF 14,15. Supernatants harvested from T lymphocytes of patients with MS cause damage to myelin and glial cells in vitro,16,17 suggesting that the MS T lymphocytes produce demyelination factors and are activated in vivo. A positive correlation also has been found between the percentage of IL-2 receptor-bearing lymphocytes and the degree of supernatant-induced in vitro demyelination.…”

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confidence: 99%

Optic Neuritis in Different Strains of Mice by a Recombinant HSV-1 Expressing Murine Interleukin-2

Zandian

Belisle

Mott

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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Purpose The authors have shown previously that a recombinant HSV-1 that constitutively expresses two copies of murine IL-2 (HSV-IL-2) induces demyelination by activated CD8+ T cells in the brain and spinal cord of ocularly infected female BALB/c mice. The present study was conducted to determine whether the ocular infection with this recombinant virus induces optic neuritis independent of virus dose, major histocompatibility complex (MHC) background, or sex. Methods Female BALB/c, C57BL/6, SJL/6, and 129SVE mice and male BALB/c mice were ocularly infected with different doses of recombinant HSV-IL-2 virus. Demyelination of optic nerves in infected mice was monitored histologically using Luxol fast blue staining and by measurement of visual-evoked cortical potentials (VECPs). Results Both focal and diffuse regions of demyelination of the optic nerves were observed in the HSV-IL-2–infected mice as early as day 10 after infection and as late as day 60 after infection (the final experimental time point) in all strains of mice tested. Optic nerve demyelination was not observed in control mice ocularly infected with HSV-IL-4 or wild-type HSV-1. VECP responses were delayed significantly in the HSV-IL-2–infected mice compared with mice infected with control viruses. Conclusions The results demonstrate for the first time that a combination of viral infection and constitutive expression of IL-2, but not IFN-γ or IL-4, can result in demyelination and visual impairment in the optic nerves of ocularly infected mice.

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“…These clinical findings of elevated IL-2 levels (and lower than normal IL-4 levels) in the sera of MS patients suggest a possible link between IL-2 and the onset of MS. Furthermore, supernatants harvested from T lymphocytes of MS patients cause damage to myelin and glial cells in vitro (11,12), suggesting that the MS T lymphocytes produce demyelination factors and are activated in vivo.In order to investigate the role of cytokines in demyelination in a viral model of MS, we had constructed a panel of recombinant herpes simplex virus 1 (HSV-1) isolates that constitutively express murine cytokines, including IL-2 (13), IL-4, gamma interferon (IFN-␥), . Using these viruses, we have shown that infection of different strains of mice with a recombinant HSV-1 strain constitutively expressing IL-2 (HSV-IL-2), but not HSV-IL-4, HSV-IFN-␥, HSV-IL-12p35, or HSV-IL12p40, results in demyelination of the optic nerves (ONs), the spinal cords (SCs), and the brains of the infected mice, as determined by histologic examination of tissues obtained at necropsy (17,18).…”

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confidence: 99%

mentioning

confidence: 99%

Role of Interleukin-2 and Herpes Simplex Virus 1 in Central Nervous System Demyelination in Mice

Mott

Zandian

Allen

et al. 2013

J Virol

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We have reported previously that ocular infection of different strains of mice with recombinant herpes simplex virus 1 (HSV-1) constitutively expressing interleukin-2 (IL-2) provokes central nervous system (CNS) demyelination and optic neuropathy, as determined by changes in visual evoked cortical potentials and pathological changes in the optic nerve and CNS, whereas recombinant viruses expressing IL-4, gamma interferon, IL-12p35, IL-12p40, or IL-12p70 do not induce this neuropathy. The goal of this study was to dissect the mechanism underlying the interplay between the immune system (elevation of IL-2) and an environmental factor (infection with HSV-1) that elicits this pathology. Similar results were obtained upon delivery of IL-2 into the mouse brain using osmotic minipumps or injection of mice with recombinant IL-2 protein, IL-2 DNA, or IL-2 synthetic peptides prior to infection with wild-type (wt) HSV-1 strains McKrae and KOS. The critical role of IL-2 is further supported by our data, indicating that a single mutation at position T27A in IL-2 completely blocks the HSV-1-induced pathology. This study shows a novel model of autoimmunity in which viral infection and enhanced IL-2 cause CNS demyelination. Several lines of evidence implicate interleukin-2 (IL-2) in the pathology of multiple sclerosis (MS) (1-4). Patients with MS have elevated levels of IL-2 in their sera and cerebrospinal fluid (CSF) (1-4). The soluble IL-2 receptor (sIL-2R) is also elevated in the sera and CSF of patients with MS (3, 5-10). These clinical findings of elevated IL-2 levels (and lower than normal IL-4 levels) in the sera of MS patients suggest a possible link between IL-2 and the onset of MS. Furthermore, supernatants harvested from T lymphocytes of MS patients cause damage to myelin and glial cells in vitro (11,12), suggesting that the MS T lymphocytes produce demyelination factors and are activated in vivo.In order to investigate the role of cytokines in demyelination in a viral model of MS, we had constructed a panel of recombinant herpes simplex virus 1 (HSV-1) isolates that constitutively express murine cytokines, including IL-2 (13), IL-4, gamma interferon (IFN-␥), . Using these viruses, we have shown that infection of different strains of mice with a recombinant HSV-1 strain constitutively expressing IL-2 (HSV-IL-2), but not HSV-IL-4, HSV-IFN-␥, HSV-IL-12p35, or HSV-IL12p40, results in demyelination of the optic nerves (ONs), the spinal cords (SCs), and the brains of the infected mice, as determined by histologic examination of tissues obtained at necropsy (17,18). In addition, the HSV-IL-2-infected mice developed optic neuropathy, as determined by changes in the visual evoked cortical potentials (VECPs) (18). Using knockout mice, depletion, and transfer studies, we found that both CD8 ϩ and CD4 ϩ T cells contributed to HSV-IL-2-induced central nervous system (CNS) demyelination, with CD8 ϩ T cells being the primary inducers (19). We have also found that infection of mice with a recombinant HSV-1 isolate expressing IL-12p...

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Interleukin-1 and interleukin-2 production by peripheral blood mononuclear cells in multiple sclerosis patients

Cited by 26 publications

References 31 publications

Lymphocyte activating factor activity in the serum and cerebrospinal fluid of patients with multiple sclerosis

Lymphocyte activating factor activity in the serum and cerebrospinal fluid of patients with multiple sclerosis

Optic Neuritis in Different Strains of Mice by a Recombinant HSV-1 Expressing Murine Interleukin-2

Role of Interleukin-2 and Herpes Simplex Virus 1 in Central Nervous System Demyelination in Mice

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