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Open Access Research article

Preliminary study: Treatment with intramuscular interferon beta-1a results in increased levels of IL-12Rβ2+ and decreased levels of IL23R+ CD4+ T - Lymphocytes in multiple sclerosis

Jennifer M Kress-Bennett1, Garth D Ehrlich123, Ashley Bruno4, J Christopher Post123, Fen Z Hu123* and Thomas F Scott45

Author Affiliations

1 Center for Genomic Sciences, Allegheny-Singer Research Institute, 320 East North Avenue, Pittsburgh, PA 15212, USA

2 Department of Microbiology and Immunology, Drexel University College of Medicine, Allegheny Campus, 320 East North Avenue, Pittsburgh, PA 15212, USA

3 Department of Otolaryngology-Head and Neck Surgery, Drexel University College of Medicine, Allegheny Campus, 320 East North Avenue, Pittsburgh, PA 15212, USA

4 Department of Neurology, Allegheny General Hospital, 320 East North Avenue, East Wing, Pittsburgh PA, 15212; USA

5 Department of Neurology, Drexel University College of Medicine, Allegheny Campus, 320 East North Avenue, Pittsburgh, PA 15212, USA

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BMC Neurology 2011, 11:155  doi:10.1186/1471-2377-11-155

Published: 19 December 2011

Abstract

Background

There are a lack of biomarkers which can be used to predict clinical outcomes for multiple sclerosis (MS) patients receiving interferon beta (IFN-β). Thus the objective of this study was to characterize changes in CD4+ T-lymphocyte expression in an unbiased manner following initiation of intramuscular (IM) IFN-β-1a treatment, and then to verify those findings using marker-specific assays.

Methods

Peripheral blood specimens were collected from twenty MS patients before and after treatment with intramuscular (IM) IFN-β-1a and were used for isolation of mononuclear cells (PBMCs). mRNA expression patterns of negatively-selected CD4+ T-cells from the PBMCs were analyzed using microarray gene expression technology. IL-12 and IL-23 receptor levels on PBMC-derived CD4+ T-cells were analyzed by flow cytometry. The phosphorylation status of Stat4 was measured by performing densitometry on western blots.

Results

Microarray analyses demonstrated that mRNA expression of the IL-12Rβ2 gene was uniformly up-regulated in response to IFN-β-1a treatment and was associated with an increased number of IL-12Rβ2+ CD4+ T-cells by flow cytometry in 4 of 6 patients. This finding was substantiated by demonstrating that Stat4 phosphorylation, a transcription factor for IL-12, was increased after treatment. Conversely, the number of IL-23R+ CD4+ T-cells was decreased following treatment.

Conclusions

The IL-12 receptor shares a common subunit, the IL-12Rβ2, with the IL-23 receptor. Both of these receptors have a probable role in regulating IL-17 and TH-17 cells, important mediators of inflammation in multiple sclerosis (MS). Thus, the changes in the numbers of CD4+ T-cells expressing these receptors in response to IFN-β-1a treatment may point to an important mechanism of action for this drug, but further large scale studies are needed to confirm these preliminary observations.