EFFECT OF CYCLOPHOSPHAMIDE ON LEUKOCYTIC INFILTRATION IN THE BRAIN OFMRL 1PR MICE/

Neuropsychiatric manifestations are a poorly understood and potentiall y life-threatening complication of systemic lupus erythematosus (SLE). MRL/lpr mice spontaneously develop a lupus-like syndrome which is sim ilar to the human disease in many respects, including behavioural abno rmalities. Our previous findings indicated that the age at which infil tration of immune cells into the choroid plexus is first observed coin cides with the appearance of behavioural dysfunction in MRL/lpr mice. This present study quantified leukocyte infiltration in relation to pr olonged 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 cel ls (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.) sig nificantly 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 ha s 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.