Treatment of Multiple Sclerosis with Methylprednisolone and Mitoxantrone Modulates the Expression of CXC Chemokine Receptors in PBMC Bartosz Bielecki & Andzelika Mazurek & Pawel Wolinski & Andrzej Glabinski Received: 14 August 2007 / Accepted: 2 October 2007 / Published online: 25 October 2007 # Springer Science + Business Media, LLC 2007 Abstract Chemokines and their receptors are involved in the development of multiple sclerosis (MS). Methylpred- nisolone (MP) and mitoxantrone (MTX) are commonly used in the treatment of MS. In this study, we analyzed the expression of chemokine receptors CXCR1, CXCR2, CXCR3, CXCR4, and CXCR5 in peripheral blood mononuclear cells (PBMC) from MS patients before and after treatment with MP or MTX. We observed a significant upregulation of expression of CXCR1 and CXCR2 in untreated MS patients. Treatment of MS with MP stimulated further increase of expression of both receptors. Therapy for MS with MTX resulted in decrease of CXCR2 expression. There was a negative correlation between the expression of CXCR1 and CXCR2 and the cumulative dose of MTX received by patients. These results suggest that CXCR1 and CXCR2 may be involved in MS pathogenesis and that treatment of this disease with MP and MTX may influence expression of those receptors. Keywords Multiple sclerosis . CXCR1 . CXCR2 . mitoxantrone . methylprednisolone Introduction Despite intensive efforts of researchers and clinicians, multiple sclerosis (MS) remains the most frequent neurological disease of the central nervous system (CNS) leading to progressive disability of young adults. Pathogenesis of MS is so far not fully understood. A number of different factors play a role in the development of this disease, including genetic susceptibility [1]. Many data supported by experiments using animal models of MS like experimental autoimmune encephalomyelitis (EAE) suggest that autoimmune-mediated inflammation in the CNS is a key event responsible for the development of this disease [2]. Early pathology of both MS and EAE is characterized by the presence of disseminated inflamma- tory lesions and demyelination in the CNS. Most of the lesions can be found in the periventricular white matter, optic nerves, cerebellum, brain stem, and spinal cord white matter. Initial events during the development of the CNS inflam- mation are still disputable. It is proposed that the early presence of activated autoreactive T cell in the CNS infiltrates is linked with the local secretion of predominantly Th1 cytokines including TNF alpha, IL-1, IL-2, IL-12, IFN gamma [3]. Subsequent breakdown of the blood–brain barrier (BBB) leads to the further influx of inflammatory cells to the CNS parenchyma with the successive destruction of myelin sheath. Inflammatory lesions contain mainly CD4(+) and CD8(+) T cells and macrophages, but B cells can also be found within the CNS infiltrates [2]. Demyelination is a hallmark of white matter damage during the neuroinflammation in MS and EAE, and it also leads to the progressive loss of axons. Axonal damage is observed already at the early clinical stage of MS, which is confirmed by MRI data [4]. Axonal pathology is a result of many processes, including J Clin Immunol (2008) 28:122–130 DOI 10.1007/s10875-007-9142-7 B. Bielecki : A. Mazurek : P. Wolinski : A. Glabinski (*) Department of Experimental and Clinical Neurology, Medical University of Lodz, Mazowiecka Str. 6/8 92-215, Lodz, Poland e-mail: aglabinski@poczta.onet.pl B. Bielecki : A. Glabinski Department of Neurology, Medical University of Lodz, Kopcinskiego Str. 22 90-153, Lodz, Poland