J Neuroimmunol. 2003 Sep;142(1-2):75-85
Eltayeb S, Sunnemark D, Berg AL, Nordvall G, Malmberg A, Lassmann H,
Wallstrom E, Olsson T, Ericsson-Dahlstrand A.
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-1alpha) 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.