Effect of cyclophosphamide on leukocytic infiltration in the brain of MRL/lpr mice.
Neuropsychiatric manifestations are a poorly understood and potentially life-threatening complication of systemic lupus erythematosus (SLE). MRL/lpr mice spontaneously develop a lupus-like syndrome which is similar to the human disease in many respects, including behavioural abnormalities. Our previous findings indicated that the age at which infiltration of immune cells into the choroid plexus is first observed coincides with the appearance of behavioural dysfunction in MRL/lpr mice. This present study quantified leukocyte infiltration in relation to prolonged administration of cyclophosphamide (CY), a treatment effective in preventing some behavioural deficits. Compared to MRL +/+ controls, saline-treated MRL/lpr mice had significantly more CD45-positive cells (leukocytes) and CD45R-positive (B) cells in the choroid plexus and in the brain parenchyma. A six week course of CY (100 mg/kg i.p.) significantly reduced the infiltration of CD45, but not of CD45R-positive cells into the choroid plexus of the MRL/lpr substrain. In addition, the presence of leukocytes correlated positively with measures on one behavioural test (floating in the forced swim test) but not on another test (novel object test). These findings suggest that CY treatment has a differential effect on the infiltration of leukocyte subtypes and strengthen the hypothesis that some abnormal behaviour in MRL/lpr mice may be related to the presence of immunocompetent cells in the brain.
Farrell
M
M
Department of Medicine, McMaster University, Hamilton, ON.
Sakić
B
B
Szechtman
H
H
Denburg
J A
JA
D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002831:Choroid Plexus / Q000187:drug effects / Q000473:pathology*; D003520:Cyclophosphamide / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017493:Leukocyte Common Antigens / Q000032:analysis; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000145:classification / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D013550:Swimming
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D017493:Leukocyte Common Antigens