Induction of mRNA for tumor necrosis factor-alpha and interleukin-1 beta in mice brain, spleen and liver in an animal model of Shigella-related seizures

Background: The pathogenesis of neurological symptoms, the most common extr aintestinal complication of childhood shigellosis, is unclear. To elucidate the mechanisms involved, we developed an animal model and demonstrated tha t TNF alpha and IL-1 beta play a role. Objectives: To determine whether TNF alpha and IL-1 beta genes are expresse d in the brain following peripheral administration Shigella dysenteriae 60R . Methods: Expression of mRNA for TNF alpha and IL-1 beta was examined in the brain structures (hypothalamus and hippocampus) and peripheral organs by r everse transcriptase polymerase chain reaction, at different time points af ter intraperitoneal injection of S. dysenteriae sonicate. Results: In our anima! model of Shigella-related seizures, TNF alpha and IL -1 beta mRNA were induced in the brain, spleen and liver already 1 hour aft er injection of S. dysenteriae sonicate. The expression of TNF alpha and IL -1 beta mRNA in spleen, hippocampus and hypothalamus decreased after 6 h an d increased again at 18 h post-injection. Conclusions: Local production of TNF alpha and IL-1 beta in the brain may b e involved in the enhanced seizure response of mice after administration of S. dysenteriae. It is possible that intracerebral production of TNF alpha and IL-1 beta plays a role in neurological disturbances of human shigellosi s.