2004 IMFAR Abstract

Maternal exposure to IL-2 induces long-lasting behavior-inducing effects in offspring  

J. Hu, A. Rossi, M. Bobbin, S. Cutro, S. Zalcman and N.M. Ponzio*. Departments of Psychiatry and Pathology. UMDNJ – New Jersey Medical School and Graduate School of Biomedical Sciences, Newark, NJ 07103

Maternal immune activation is thought to play a role in the etiology of autism spectrum disorder (ASD). We demonstrated that interleukin (IL)-2, a T helper 1-derived cytokine, significantly influences locomotion and exploratory activity in adult male mice tested in an unfamiliar environment (Zalcman et al., 1998). Furthermore, mice given repeated injections of IL-2 (once a day for 5 days) display marked increases in stereotypical motor activity (Zalcman, 2002). IL-2 treatment also produces a long-lasting increase in sensitivity to the behavior-activating effects of a highly selective dopamine uptake inhibitor, suggesting that increases in this cytokine can have long-term psychopathological effects (Zalcman, 2001). In light of evidence that maternal immune activation can influence the development of behavioral abnormalities characteristic of certain dimensions of autism spectrum disorder, we hypothesized that maternal exposure to IL-2 would induce long-term behavior-activating effects in offspring. Pregnant SJL/J mice were injected with vehicle or IL-2 (0.4 mg/mouse; one injection/day for 5 days).  When tested as adults, offspring of IL-2-treated dams displayed marked increases in locomotion and rearing behavior. Male offspring appeared particularly vulnerable to this effect. The magnitude of the increases in motor activity was similar to that induced by IL-2 in adult mice. These data suggest that increases in maternal levels of IL-2 during pregnancy can result in long-term behavioral abnormalities in offspring, particularly in male mice.  Supported by the National Alliance for Autism Research and the New Jersey Governor’s Council on Autism.