Correlation of cytokine expression with rabies virus distribution in rabies encephalitis.

Rabies encephalitis is a significant health hazard, particularly in Asia. To understand the role of immune mechanisms and cytokines in rabies encephalitis, we performed a retrospective and prospective study on the autopsy material. Representative histopathological sections were studied and subjected to immunostaining for rabies virus antigen, TNF-alpha and IL-1beta. Immunohistochemistry for IL-1beta and TNF-alpha revealed expression of these cytokines in 96% of cases in microglial cells, macrophages and lymphocytes with a strong positive correlation between IL-1beta and TNF-alpha immunopositivity and degree of perivascular and parenchymal inflammation. In addition, expression of IL-1beta and TNF-alpha also correlated positively with each other. However there was no direct correlation of viral antigen load with grading of cytokine expression. These findings indicate that IL-1beta and TNF-alpha together may play an important role to coordinate the dramatic inflammatory response associated with the rabies-encephalopathy. They may serve as important targets for future therapy.