Long-term favorable response to interferon beta-1b is linked to cytokine deviation toward the Th2 and Tc2 sides in Japanese patients with multiple sclerosis

Feng Jun Mei, Manabu Osoegawa, Hirofumi Ochi, Motozumi Minohara, Shi Nan, Hiroyuki Murai, Takaaki Ishizu, Takayuki Taniwaki, Jun ichi Kira

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Abstract

To address the immune mechanism of the long-term beneficial effects of interferon beta (IFN-β), we measured the intracellular cytokine production patterns of IFN-γ, IL-4 and IL-13 in peripheral blood CD4+ and CD8+ T cells, which previously displayed alterations during the early course of IFN-β treatment, in 15 Japanese patients after long-term IFN-β administration. The patients were treated with IFN-β-1b 8 × 106 units given subcutaneously every other day for a mean period of 34.5 ± 5.5 months (range: 26-43 months). During the follow-up period, 6 patients experienced 33 relapses, while the other 9 were relapse-free. The results revealed the following cytokine alterations: (1) type 2 cytokine, such as IL-4 and IL-13, were significantly increased in producing cell percentages in both CD4+ (p = 0.0356 and p = 0.0007, respectively) and CD8+ (p = 0.0231 and p = 0.0170, respectively) T cells while IFN-γ, a representative type 1 cytokine, was significantly decreased in the absolute producing cell numbers (p = 0.0125 in CD4+ T cells and p = 0.0022 in CD8+ T cells) even after approximately 3 years of IFN-β administration; (2) the intracellular IFN-γ / IL-4 ratio tended to decrease in both CD4+ and CD8+ T cells (p = 0.0535 and p = 0.0783, respectively), reflecting a strong downmodulation of type 1 cytokine producing cells; and importantly (3) alterations such as the decreased intracellular IFN-γ / IL-4 ratio in CD4+ T cells and increased percentage of CD8+ IL-13+ T cells compared with the pretreatment levels were only statistically significant in MS patients without relapse during IFN-β therapy (p = 0.0152 and p = 0.0078, respectively). Therefore, we consider that cytokine deviation toward the Th2 and Tc2 sides is linked to a long-term favorable response to IFN-β, while a higher intracellular IFN-γ / IL-4 ratio is associated with treatment failure.

Original languageEnglish
Pages (from-to)71-77
Number of pages7
JournalJournal of the Neurological Sciences
Volume246
Issue number1-2
DOIs
Publication statusPublished - Jul 15 2006

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Interferon-beta
Multiple Sclerosis
Cytokines
Interleukin-4
T-Lymphocytes
Interleukin-13
Recurrence
Interferon beta-1b
Treatment Failure
Interleukin-6
Cell Count

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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Long-term favorable response to interferon beta-1b is linked to cytokine deviation toward the Th2 and Tc2 sides in Japanese patients with multiple sclerosis. / Mei, Feng Jun; Osoegawa, Manabu; Ochi, Hirofumi; Minohara, Motozumi; Nan, Shi; Murai, Hiroyuki; Ishizu, Takaaki; Taniwaki, Takayuki; Kira, Jun ichi.

In: Journal of the Neurological Sciences, Vol. 246, No. 1-2, 15.07.2006, p. 71-77.

Research output: Contribution to journalArticle

Mei, Feng Jun ; Osoegawa, Manabu ; Ochi, Hirofumi ; Minohara, Motozumi ; Nan, Shi ; Murai, Hiroyuki ; Ishizu, Takaaki ; Taniwaki, Takayuki ; Kira, Jun ichi. / Long-term favorable response to interferon beta-1b is linked to cytokine deviation toward the Th2 and Tc2 sides in Japanese patients with multiple sclerosis. In: Journal of the Neurological Sciences. 2006 ; Vol. 246, No. 1-2. pp. 71-77.
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abstract = "To address the immune mechanism of the long-term beneficial effects of interferon beta (IFN-β), we measured the intracellular cytokine production patterns of IFN-γ, IL-4 and IL-13 in peripheral blood CD4+ and CD8+ T cells, which previously displayed alterations during the early course of IFN-β treatment, in 15 Japanese patients after long-term IFN-β administration. The patients were treated with IFN-β-1b 8 × 106 units given subcutaneously every other day for a mean period of 34.5 ± 5.5 months (range: 26-43 months). During the follow-up period, 6 patients experienced 33 relapses, while the other 9 were relapse-free. The results revealed the following cytokine alterations: (1) type 2 cytokine, such as IL-4 and IL-13, were significantly increased in producing cell percentages in both CD4+ (p = 0.0356 and p = 0.0007, respectively) and CD8+ (p = 0.0231 and p = 0.0170, respectively) T cells while IFN-γ, a representative type 1 cytokine, was significantly decreased in the absolute producing cell numbers (p = 0.0125 in CD4+ T cells and p = 0.0022 in CD8+ T cells) even after approximately 3 years of IFN-β administration; (2) the intracellular IFN-γ / IL-4 ratio tended to decrease in both CD4+ and CD8+ T cells (p = 0.0535 and p = 0.0783, respectively), reflecting a strong downmodulation of type 1 cytokine producing cells; and importantly (3) alterations such as the decreased intracellular IFN-γ / IL-4 ratio in CD4+ T cells and increased percentage of CD8+ IL-13+ T cells compared with the pretreatment levels were only statistically significant in MS patients without relapse during IFN-β therapy (p = 0.0152 and p = 0.0078, respectively). Therefore, we consider that cytokine deviation toward the Th2 and Tc2 sides is linked to a long-term favorable response to IFN-β, while a higher intracellular IFN-γ / IL-4 ratio is associated with treatment failure.",
author = "Mei, {Feng Jun} and Manabu Osoegawa and Hirofumi Ochi and Motozumi Minohara and Shi Nan and Hiroyuki Murai and Takaaki Ishizu and Takayuki Taniwaki and Kira, {Jun ichi}",
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T1 - Long-term favorable response to interferon beta-1b is linked to cytokine deviation toward the Th2 and Tc2 sides in Japanese patients with multiple sclerosis

AU - Mei, Feng Jun

AU - Osoegawa, Manabu

AU - Ochi, Hirofumi

AU - Minohara, Motozumi

AU - Nan, Shi

AU - Murai, Hiroyuki

AU - Ishizu, Takaaki

AU - Taniwaki, Takayuki

AU - Kira, Jun ichi

PY - 2006/7/15

Y1 - 2006/7/15

N2 - To address the immune mechanism of the long-term beneficial effects of interferon beta (IFN-β), we measured the intracellular cytokine production patterns of IFN-γ, IL-4 and IL-13 in peripheral blood CD4+ and CD8+ T cells, which previously displayed alterations during the early course of IFN-β treatment, in 15 Japanese patients after long-term IFN-β administration. The patients were treated with IFN-β-1b 8 × 106 units given subcutaneously every other day for a mean period of 34.5 ± 5.5 months (range: 26-43 months). During the follow-up period, 6 patients experienced 33 relapses, while the other 9 were relapse-free. The results revealed the following cytokine alterations: (1) type 2 cytokine, such as IL-4 and IL-13, were significantly increased in producing cell percentages in both CD4+ (p = 0.0356 and p = 0.0007, respectively) and CD8+ (p = 0.0231 and p = 0.0170, respectively) T cells while IFN-γ, a representative type 1 cytokine, was significantly decreased in the absolute producing cell numbers (p = 0.0125 in CD4+ T cells and p = 0.0022 in CD8+ T cells) even after approximately 3 years of IFN-β administration; (2) the intracellular IFN-γ / IL-4 ratio tended to decrease in both CD4+ and CD8+ T cells (p = 0.0535 and p = 0.0783, respectively), reflecting a strong downmodulation of type 1 cytokine producing cells; and importantly (3) alterations such as the decreased intracellular IFN-γ / IL-4 ratio in CD4+ T cells and increased percentage of CD8+ IL-13+ T cells compared with the pretreatment levels were only statistically significant in MS patients without relapse during IFN-β therapy (p = 0.0152 and p = 0.0078, respectively). Therefore, we consider that cytokine deviation toward the Th2 and Tc2 sides is linked to a long-term favorable response to IFN-β, while a higher intracellular IFN-γ / IL-4 ratio is associated with treatment failure.

AB - To address the immune mechanism of the long-term beneficial effects of interferon beta (IFN-β), we measured the intracellular cytokine production patterns of IFN-γ, IL-4 and IL-13 in peripheral blood CD4+ and CD8+ T cells, which previously displayed alterations during the early course of IFN-β treatment, in 15 Japanese patients after long-term IFN-β administration. The patients were treated with IFN-β-1b 8 × 106 units given subcutaneously every other day for a mean period of 34.5 ± 5.5 months (range: 26-43 months). During the follow-up period, 6 patients experienced 33 relapses, while the other 9 were relapse-free. The results revealed the following cytokine alterations: (1) type 2 cytokine, such as IL-4 and IL-13, were significantly increased in producing cell percentages in both CD4+ (p = 0.0356 and p = 0.0007, respectively) and CD8+ (p = 0.0231 and p = 0.0170, respectively) T cells while IFN-γ, a representative type 1 cytokine, was significantly decreased in the absolute producing cell numbers (p = 0.0125 in CD4+ T cells and p = 0.0022 in CD8+ T cells) even after approximately 3 years of IFN-β administration; (2) the intracellular IFN-γ / IL-4 ratio tended to decrease in both CD4+ and CD8+ T cells (p = 0.0535 and p = 0.0783, respectively), reflecting a strong downmodulation of type 1 cytokine producing cells; and importantly (3) alterations such as the decreased intracellular IFN-γ / IL-4 ratio in CD4+ T cells and increased percentage of CD8+ IL-13+ T cells compared with the pretreatment levels were only statistically significant in MS patients without relapse during IFN-β therapy (p = 0.0152 and p = 0.0078, respectively). Therefore, we consider that cytokine deviation toward the Th2 and Tc2 sides is linked to a long-term favorable response to IFN-β, while a higher intracellular IFN-γ / IL-4 ratio is associated with treatment failure.

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