We investigated whether prostaglandins (PGs), proinflammatory mediators implicated in excitatory activity, are involved in Shigella-related seizures. Pretreatment with S. dysenteriae sonicate (2LD(50)) enhanced mice response to pentylenetetrazole-induced seizures, without increase of brain concentrations of PGE(2), PGD(2) or PGF(2alpha). Preinjection of NS-398, an inhibitor of cyclooxygenase-2, before treatment with Shigella sonicate, had no effect on seizures. The anticonvulsive PGD(2) increased after injection of 8 LD(50) of Shigella sonicate, which did not enhance seizures (32 pg/mg vs 26 pg/ml, p=0.0063). The findings indicate that PGs are not involved in the enhanced seizure response after exposure to Shigella. However, induction of PGD(2) may play an inhibitory role.