EAE is associated with sickness behavior symptoms that are temporally correlated with inflammatory processes. To further elucidate the role of inflammatory mediators in the behavioral syndrome, EAE mice were injected daily with anti-inflammatory drugs, beginning at disease onset. Dexamethasone or interleukin-1 (IL-1) receptor antagonist or the prostaglandins synthesis inhibitor indomethacin attenuated the behavioral symptoms. Administration of the tumor necrosis-factor α (TNF-α) synthesis inhibitor pentoxifylline or targeted deletion of the type I TNF receptor had no behavioral effects whereas administration of pentoxifylline in IL-1ra-treated mice further reversed the behavioral depression. These findings demonstrate the critical involvement of pro-inflammatory cytokines and prostaglandins in the EAE-associated behavioral syndrome, and may have implications for understanding and treating the neuropsychiatric disturbances in multiple sclerosis (MS) patients.
Bibliographical noteFunding Information:
The authors thank Orli Bar-Shalev, Shira Gur, Lior Friedman, Yael Perets, Meital Shahar, Michal Shlayer, Michal Shuker, and Gili Wolf for their excellent help in running the experiments. The research was supported by a grant from the Israel Science Foundation (No. 820/00) and in part by the Lena P. Harvey Endowment Fund for Neurological Research. RY is a member of the Eric Roland Center for Neurodegenerative Diseases at the Hebrew University of Jerusalem.
- Anti-inflammatory drugs
- Multiple sclerosis
- Pro-inflammatory cytokines
- Sickness behavior