Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus

Limbic status epilepticus was induced in rats by unilateral 60-min electric al stimulation of the CA3 region of the ventral hippocampus. As assessed by RT-PCR followed by Southern blot analysis, transcripts of interleukin-1 be ta, interleukin-6, interleukin-1 receptor antagonist and inducible nitric o xide synthase were significantly increased 2 h after status epilepticus in the stimulated hippocampus. Induction was maximal at 6 h for interleukin-1 beta (445%), interleukin-6 (405%) and tumour necrosis factor-alpha (264%) a nd at 24 h for interleukin-1 receptor antagonist (494%) and inducible nitri c oxide synthase (432%). In rats with spontaneous seizures (60 days after s tatus epilepticus), interleukin-1 beta mRNA was still higher than controls (241%). Immunocytochemical staining of interleukin-1 beta, interleukin-6 an d tumour necrosis factor-alpha was enhanced in glia with a time-course simi lar to that of the respective transcripts. Sixty days after status epilepti cus, interleukin-1 beta immunoreactivity was increased exclusively in neuro ns in one third of the animals. Multiple intracerebroventricular injections of interleukin-1 receptor antagonist (0.5 mu g/3 mu L) significantly decre ased the severity of behavioural convulsions during electrical stimulation and selectively reduced tumour necrosis factor-alpha content in the hippoca mpus measured 18 h after status epilepticus. Thus, the induction of spontan eously recurring seizures in rats involves the activation of inflammatory c ytokines and related pro- and anti-inflammatory genes in the hippocampus. T hese changes may play an active role in hyperexcitability of the epileptic tissue.