Effector stage CC chemokine receptor-1 selective antagonism reduces multiple sclerosis-like rat disease.
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.
D000818:Animals; D002464:Cell Migration Inhibition; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D007279:Injections, Subcutaneous; D008232:Lymphoproliferative Disorders / Q000139:chemically induced; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
C406591:2,2-diphenyl-(5-(4-chlorophenyl)piperidin-1-yl)valeronitrile; C515302:Ccr1 protein, rat; D019742:Chemokines, CC; D007166:Immunosuppressive Agents; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009570:Nitriles; D010879:Piperazines; D054389:Receptors, CCR1; D019707:Receptors, Chemokine