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J Neuroimmunol. 2003 Sep;142(1-2):75-85.

Effector stage CC chemokine receptor-1 selective antagonism reduces multiple sclerosis-like rat disease.

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Neuroimmunology Unit, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.


We have studied the role of the chemokine receptor CCR1 during the effector stage of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in DA rats. In situ hybridization histochemistry revealed local production of the CCR1 ligands CCL3 (MIP-1 alpha) and CCL5 (RANTES), as well as large numbers of CCR1 and CCR5 expressing cells within inflammatory brain lesions. A low-molecular weight CCR1 selective antagonist potently abrogated both clinical and histopathological disease signs during a 5-day treatment period, without signs of peripheral immune compromise. Thus, we demonstrate therapeutic targeting of CCR1-dependent leukocyte recruitment to the central nervous system in a multiple sclerosis (MS)-like rat model.

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