Treatment of Multiple Sclerosis with Methylprednisolone and Mitoxantrone Modulates the Expression of CXC Chemokine Receptors in PBMC

Abstract

Chemokines and their receptors are involved in the development of multiple sclerosis (MS). Methylprednisolone (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.

Mitoxantrone in the treatment of multiple sclerosis: a single-center experience

“…Hem immünomodülatör hem de immünsupresif etkinliği olan mitoksantron (MIT) sentetik antrosenedion türevi bir antineoplastiktir (8,9). İlk kez akut miyeloid lösemi tedavisi için onay almış olan bu ajan kötüleşen RRMS ve SPMS hastalarında, nörolojik progresyonu yavaşlattığı, atak sayısını azalttığı görülmüştür (10)(11)(12). Proenflamatuar sitokin salınımını, T ve B lenfositlerinin profilerasyonunu engelleyerek antikor sekresyonunu, ve makrofaj proliferasyonu ile antijen sunumunu azaltarak etki edip miyelin yıkımını engellemektedir (11)(12)(13)(14)(15)(16).…”

“…Ancak farklı merkezlerde farklı uygulama protokolleri söz konusudur. Toplam 120 mg'ı geçmeyecek şekilde ayda bir defa 20 mg, 12 mg/m 2 dozunda 6 ay süre ile ayda bir ya da 2 yıl süre ile 3 ayda bir ya da ilk 6 ay 6 haftada bir sonrasında toplam 4 kez olacak şekilde 3 ayda bir uygulanabilmektedir (12,19,21).…”

Chemokine Receptors in Inflammatory Diseases

“…Subsequently, axonal injury occurs, resulting in impairment of the signal conduction of the affected neurons, leading to both physical and cognitive disability [207][208][209][210]. The infiltration of mainly T lymphocytes and macrophages in the brain causes the destruction of the myelin sheaths of neurons and the apoptosis of oligodendrocytes (myelin-forming cells).…”

“…The infiltration of mainly T lymphocytes and macrophages in the brain causes the destruction of the myelin sheaths of neurons and the apoptosis of oligodendrocytes (myelin-forming cells). The cause of multiple sclerosis is still unknown; genetic risk factors, environmental factors and auto-immune inflammatory mechanisms are under investigation for their role in the pathogenesis of this disease [207,209,211,212]. Lesions in multiple sclerosis are mainly found in the optic nerves, brain stem and in the white matter of both periventricular regions and the spinal cord [207][208][209][210][211].…”

Chemokine receptor CXCR2: Physiology regulator and neuroinflammation controller?

“…The suggested positive effect of chemokine signaling blockade range from drugs preventing cancer metastasis or ameliorating multiple sclerosis (MS) symptoms, to treatments inhibiting HIV or medications acting on roughly any other disease in which the chemokines and/or chemokine receptors have been implicated (Bielecki et al, 2008; Charo and Ransohoff, 2006; Garin and Proudfoot, 2011; Singh et al, 2010; Vasilescu et al, 2007). Research in academia and pharmaceutical industry has vastly expanded since the roles of chemokines and chemokine receptors in immunity unraveled.…”