Involvement of Tumor Necrosis Factor Alpha and Interleukin-1β in Enhancement of Pentylenetetrazole-Induced Seizures Caused by Shigella dysenteriae

Neurologic manifestations, mainly convulsions, are the most frequent extraintestinal complications of shigellosis. We used an animal model to study the roles of tumor necrosis factor alpha (TNF-α) and interleukin-1 β (IL-1β) in Shigella-related seizures. Administration of Shigella dysenteriae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pentylenetetrazole (PTZ) within 7 h. This was indicated by a significantly higher mean convulsion score and an increased number of mice responding with clonic-tonic seizures in the Shigella-pretreated group. Preinjection of mice with anti-murine TNF-α (anti-mTNF-α) or anti-murine IL-1β (anti-mIL-1β) 30 min prior to administration of Shigella sonicate abolished their enhanced response to PTZ at 7 h. Mean convulsion scores were reduced by anti-mTNF-α from 1.2 to 0.8 (P = 0.017) and by anti-mIL-1β from 1.3 to 0.7 (P = 0.008). Preinjection of anti-mTNF-α also reduced the percentage of mice responding with clonic-tonic seizures, from 48 to 29% (P = 0.002), and preinjection of anti-mIL-1β reduced it from 53 to 21% (P = 0.012). Neutralization of TNF-α or IL-1β did not protect the mice from death due to S. dysenteriae 60R. These findings indicate that TNF-α and IL-1β play a role in the very early sensitization of the central nervous system to convulsive activity after S. dysenteriae administration. Similar mechanisms may trigger neurologic disturbances in other infectious diseases.