Cytokine changes during interferon-beta therapy in multiple sclerosis: Correlations with interferon dose and MRI response

Jerome J. Graber; David Ford; Min Zhan; Gordon Francis; Hillel Panitch; Suhayl Dhib-Jalbut

doi:10.1016/j.jneuroim.2007.01.011

Cytokine changes during interferon-beta therapy in multiple sclerosis: Correlations with interferon dose and MRI response

Jerome J. Graber, David Ford, Min Zhan, Gordon Francis, Hillel Panitch, Suhayl Dhib-Jalbut

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

We investigated serum (IL-10 and IL-12p70) and cellular cytokine levels (IL-10, IL-12p40, IL-12p70, IFN-γ) in stimulated PBMC over 24 weeks in 15 relapsing-remitting multiple sclerosis (MS) patients randomized to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) (n = 8) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) (n = 7). Overall, IFN-β treatment increased cellular IL-10 (p < 0.01) levels and the ratios of cellular IL-10/IL-12p40 (p < 0.01) and IL-10/IL-12p70 (p < 0.02) while cellular IFN-γ levels were reduced (p < 0.01). Serum IL-10 levels were decreased in non-responders to therapy based on MRI-defined criteria (p < 0.01) but did not change in responders over the course of treatment. In addition, non-responders demonstrated a decrease in serum IL-10/IL-12p70 ratio (p = 0.031) and a decrease in cellular IL-12p70 (p < 0.02). A decrease in cellular IFN-γ was observed in responders (p = 0.013). This is the first study that compares cytokine changes between the two IFN-β regimes and demonstrates that serum IL-10 levels decrease in those patients who continue to have active MRI lesions while on interferon-beta therapy.

Original language	English (US)
Pages (from-to)	168-174
Number of pages	7
Journal	Journal of Neuroimmunology
Volume	185
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2007.01.011
State	Published - Apr 2007
Externally published	Yes

Keywords

Biomarker
Interferon-beta
Interferon-gamma
Interleukin-10
Interleukin-12
Multiple sclerosis

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

Access to Document

10.1016/j.jneuroim.2007.01.011

Cite this

@article{c0059fa6199b49698d8f06c9394ad037,

title = "Cytokine changes during interferon-beta therapy in multiple sclerosis: Correlations with interferon dose and MRI response",

abstract = "We investigated serum (IL-10 and IL-12p70) and cellular cytokine levels (IL-10, IL-12p40, IL-12p70, IFN-γ) in stimulated PBMC over 24 weeks in 15 relapsing-remitting multiple sclerosis (MS) patients randomized to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) (n = 8) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) (n = 7). Overall, IFN-β treatment increased cellular IL-10 (p < 0.01) levels and the ratios of cellular IL-10/IL-12p40 (p < 0.01) and IL-10/IL-12p70 (p < 0.02) while cellular IFN-γ levels were reduced (p < 0.01). Serum IL-10 levels were decreased in non-responders to therapy based on MRI-defined criteria (p < 0.01) but did not change in responders over the course of treatment. In addition, non-responders demonstrated a decrease in serum IL-10/IL-12p70 ratio (p = 0.031) and a decrease in cellular IL-12p70 (p < 0.02). A decrease in cellular IFN-γ was observed in responders (p = 0.013). This is the first study that compares cytokine changes between the two IFN-β regimes and demonstrates that serum IL-10 levels decrease in those patients who continue to have active MRI lesions while on interferon-beta therapy.",

keywords = "Biomarker, Interferon-beta, Interferon-gamma, Interleukin-10, Interleukin-12, Multiple sclerosis",

author = "Graber, {Jerome J.} and David Ford and Min Zhan and Gordon Francis and Hillel Panitch and Suhayl Dhib-Jalbut",

note = "Funding Information: This work was supported in part by USPHS training grant HL07612–15 (Dr. Graber), Serono, Inc., and The National Institute of Neurological Disorders and Stroke grant K-24-NS02082 (Dr. Dhib-Jalbut). The authors wish to thank Ms. Rameeza Allie, Dr. Tapas Makar, and Dr. Peter A. Calabresi for their helpful advice and technical support during the course of this project. The authors wish to thank Dr. Jordan Warnick and the Office of Student Research of the University of Maryland at Baltimore School of Medicine for supporting this research. In addition, the authors would also like to sincerely thank the individuals who volunteered to be subjects in this clinical trial, without whom this work could never have been conducted.",

year = "2007",

month = apr,

doi = "10.1016/j.jneuroim.2007.01.011",

language = "English (US)",

volume = "185",

pages = "168--174",

journal = "Journal of Neuroimmunology",

issn = "0165-5728",

publisher = "Elsevier",

number = "1-2",

}

TY - JOUR

T1 - Cytokine changes during interferon-beta therapy in multiple sclerosis

T2 - Correlations with interferon dose and MRI response

AU - Graber, Jerome J.

AU - Ford, David

AU - Zhan, Min

AU - Francis, Gordon

AU - Panitch, Hillel

AU - Dhib-Jalbut, Suhayl

N1 - Funding Information: This work was supported in part by USPHS training grant HL07612–15 (Dr. Graber), Serono, Inc., and The National Institute of Neurological Disorders and Stroke grant K-24-NS02082 (Dr. Dhib-Jalbut). The authors wish to thank Ms. Rameeza Allie, Dr. Tapas Makar, and Dr. Peter A. Calabresi for their helpful advice and technical support during the course of this project. The authors wish to thank Dr. Jordan Warnick and the Office of Student Research of the University of Maryland at Baltimore School of Medicine for supporting this research. In addition, the authors would also like to sincerely thank the individuals who volunteered to be subjects in this clinical trial, without whom this work could never have been conducted.

PY - 2007/4

Y1 - 2007/4

N2 - We investigated serum (IL-10 and IL-12p70) and cellular cytokine levels (IL-10, IL-12p40, IL-12p70, IFN-γ) in stimulated PBMC over 24 weeks in 15 relapsing-remitting multiple sclerosis (MS) patients randomized to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) (n = 8) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) (n = 7). Overall, IFN-β treatment increased cellular IL-10 (p < 0.01) levels and the ratios of cellular IL-10/IL-12p40 (p < 0.01) and IL-10/IL-12p70 (p < 0.02) while cellular IFN-γ levels were reduced (p < 0.01). Serum IL-10 levels were decreased in non-responders to therapy based on MRI-defined criteria (p < 0.01) but did not change in responders over the course of treatment. In addition, non-responders demonstrated a decrease in serum IL-10/IL-12p70 ratio (p = 0.031) and a decrease in cellular IL-12p70 (p < 0.02). A decrease in cellular IFN-γ was observed in responders (p = 0.013). This is the first study that compares cytokine changes between the two IFN-β regimes and demonstrates that serum IL-10 levels decrease in those patients who continue to have active MRI lesions while on interferon-beta therapy.

AB - We investigated serum (IL-10 and IL-12p70) and cellular cytokine levels (IL-10, IL-12p40, IL-12p70, IFN-γ) in stimulated PBMC over 24 weeks in 15 relapsing-remitting multiple sclerosis (MS) patients randomized to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) (n = 8) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) (n = 7). Overall, IFN-β treatment increased cellular IL-10 (p < 0.01) levels and the ratios of cellular IL-10/IL-12p40 (p < 0.01) and IL-10/IL-12p70 (p < 0.02) while cellular IFN-γ levels were reduced (p < 0.01). Serum IL-10 levels were decreased in non-responders to therapy based on MRI-defined criteria (p < 0.01) but did not change in responders over the course of treatment. In addition, non-responders demonstrated a decrease in serum IL-10/IL-12p70 ratio (p = 0.031) and a decrease in cellular IL-12p70 (p < 0.02). A decrease in cellular IFN-γ was observed in responders (p = 0.013). This is the first study that compares cytokine changes between the two IFN-β regimes and demonstrates that serum IL-10 levels decrease in those patients who continue to have active MRI lesions while on interferon-beta therapy.

KW - Biomarker

KW - Interferon-beta

KW - Interferon-gamma

KW - Interleukin-10

KW - Interleukin-12

KW - Multiple sclerosis

UR - http://www.scopus.com/inward/record.url?scp=33947681258&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947681258&partnerID=8YFLogxK

U2 - 10.1016/j.jneuroim.2007.01.011

DO - 10.1016/j.jneuroim.2007.01.011

M3 - Article

C2 - 17328965

AN - SCOPUS:33947681258

SN - 0165-5728

VL - 185

SP - 168

EP - 174

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1-2

ER -

Cytokine changes during interferon-beta therapy in multiple sclerosis: Correlations with interferon dose and MRI response

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this