dThis study aimed to investigate the expression of interleukin-6 (IL-6) in acute and chronic herpes simplex virus encephalitis. In the brain of 15 SJL mice infected with herpes simplex virus type 1, strain F, and 14 control animals we performed a sequential quantitative analysis of expression of IL-6 mRNA with reverse transcription real-time polymerase chain reaction. The viral burden peaked in the acute disease, and then returned to a low baseline value. At day 7 following infection, IL-6 expression was significantly (2.05-fold) increased as compared with the baseline expression in uninfected animals. Twenty-one days after infection the mRNA expression still was significantly (1.78-fold) upregulated. No significant differences of IL-6 mRNA expression between infected and control mice were found after 2 and 6 months. We observed a 2.5-fold increase of IL-6 mRNA expression in control mice with increasing age of animals. We have additionally studied the clinical evolution of HSVE in IL-6 deficient mice. In experimental herpes simplex virus encephalitis IL-6, as a potent mediator of neuronal injury, is upregulated in the acute but not in the chronic disease. IL-6 deficient mice presented early and severe clinical signs of HSVE as compared to the wild-type C57/b16 mice. (C) 2004 Elsevier Ireland Ltd. All rights reserved.