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Sabine Cepok, PhD; Herbert Schreiber, MD; Steve Hoffmann, MD; Dun Zhou, MD; Oliver Neuhaus, MD; Gloria von Geldern, MD; Sonja Hochgesand; Stefan Nessler, MD; Veith Rothhammer, MD; Michael Lang, MD; Hans-Peter Hartung, MD; Bernhard Hemmer, MD

Arch Neurol. 2009;66(10):1216-1223. Published online August 10, 2009 (doi:10.1001/archneurol.2009.138).

Background  Interferon beta has been approved for the treatment of multiple sclerosis (MS). It is believed that immunomodulatory rather than antiviral activity of interferon beta is responsible for disease amelioration. The impact of interferon beta on the chemoattraction of immune cells has not been fully addressed.

Objective  To address the influence of interferon beta on the expression of chemokines and their receptors in a standardized setting.

Design  The expression of 14 chemokines and 14 chemokine receptor genes was determined by quantitative real-time polymerase chain reaction from fresh blood samples.

Setting  Outpatient units in Germany.

Patients  Untreated and interferon beta–treated patients with MS who tested positive and negative for neutralizing antibodies (NABs) were recruited from August 24, 2006, through December 15, 2006, for the initial study and from March 12, 2007, through April 2, 2007, for the validation study.

Main Outcome Measures  Gene expression and serum chemokine protein levels.

Results  CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1 gene expression was strongly upregulated in interferon beta–treated, NAB-negative MS patients. In contrast, gene expression in interferon beta–treated, NAB-positive MS patients did not differ from untreated control donor individuals. Antibody titers inversely correlated with chemokine and chemokine receptor gene expression. Accordingly, serum chemokine protein levels of interferon beta–treated, NAB-negative MS patients were significantly higher than in untreated or interferon beta–treated, NAB-positive MS patients.

Conclusions  We demonstrate that interferon beta strongly upregulates a set of chemokines and CCR1 in peripheral immune cells. The peripheral upregulation of these chemokines may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta.

Author Affiliations: Department of Neurology, Klinikum rechts der Isar, Technische Universität, München (Drs Cepok, Nessler, Rothhammer, and Hemmer), MS Practice Study Group, Ulm (Drs Schreiber and Lang), Interdisciplinary Center for Bioinformatics, Leipzig (Dr Hoffmann), and Department of Neurology, Heinrich Heine University, Düesseldorf (Drs Zhou, Neuhaus, von Geldern, and Hartung and Ms Hochgesand), Germany.

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