Relationship between the development of autoimmunity and sensorimotor gating in MRL-Ipr mice with reduced IL-2 production

MRL-Ipr mice develop systemic lupus-like autoimmune disease associated with changes in emotional reactivity and spatial learning and memory. Although the major immunological deficit in MRL-Ipr mice is uncontrolled lymphoproliferation associated with a Fas gene mutation, these mice have a marked deficit in interleukin-2 (IL-2) production which, when treated, can prevent the development of autoimmune disease. Moreover, both MRL-Ipr and IL-2 knockout mice manifest alterations in hippocampal cytoarchitecture and cognitive behavior. We found previously that IL-2 knockout mice have alterations in prepulse inhibition (PPI), a measure of sensorimotor gating. Thus, the present study sought to test the hypothesis that that PPI would be altered in MRL-Ipr mice. Compared to MRL+/+ control mice, MRL-Ipr mice exhibited different patterns of PPI during development. Whereas 7 and 12-week MRL-Ipr mice with evidence of autoimmune disease (the onset and early stages, respectively) showed increased PPI, 5 week predisease MRL-Ipr mice did not. MRL-Ipr mice also exhibited increased acoustic startle reactivity that was independent of autoimmune disease. These behavioral changes were not associated with increased brain expression of the proinflammatory cytokines genes, IL-1 a and IL-6 CID3, or c-myc-associated apoptosis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.