Cytokine production in brain of mice experimentally infected with dengue virus.

Dengue virus encephalopathy was experimentally induced in newborn mice by i.p. inoculation of dengue 2 virus. At 6 and 9 days post-infection, motor incoordination and posterior limb paralysis were observed with focal necrosis, apoptotic cells, perivascular inflammatory cuffing and astrocytosis, mainly in the cortex and hippocampus. Expression of dengue virus genome and mRNA encoding for TNF-alpha, IL-1alpha, IL-2, IL-6, IL-1beta, IL-12 p40, IFNalpha, and IFNbeta; in addition host survival and inflammatory response genes MAC-1, EB22, GFAP, ICAM-1 and A20, were increased, suggesting that experimental dengue encephalitis could be associated with virus replication, inflammatory cytokine production or both. Similar findings have been observed in human dengue virus infection. Therefore, our results can be useful to elucidate and support the physiopathology of the disease.