Involvement of tumor necrosis factor alpha and interleukin-1 beta in enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae

Neurologic manifestations, mainly convulsions, are the most frequent extrai ntestinal complications of shigellosis. We used an animal model to study th e roles of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta ( IL-1 beta) in Shigella-related seizures. Administration of Shigella dysente riae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pen tylenetetrazole (PTZ) within 7 h. This was indicated by a significantly hig her mean convulsion score and an increased number of mice responding with c lonic-tonic seizures in the Shigella-pretreated group. Preinjection of mice with anti murine TNF-alpha (anti-mTNF-alpha) or anti-murine IL-1 beta (ant i-mIL-1 beta) 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-alpha from 1.2 to 0.8 (P = 0.017) and by anti-mIL-1 beta from 1.3 to 0.7 (P = 0.008). Preinjection of anti-mTNF-alpha also reduced the p ercentage of mice responding with clonic-tonic seizures, from 48 to 29% (P = 0.002), and preinjection of anti-mIL-1 beta reduced it from 53 to 21% (P = 0.012). Neutralization of TNF-alpha or IL-1 beta did not protect the mice from death due to S. dysenteriae 60R. These findings indicate that TNF-alp ha and IL-1 beta 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.