The role of macrophage migration inhibitory factor in alphaviral induced inflammatory disease

Abstract

Introduction Ross River virus (RRV), an alphavirus of the family Togaviridae, circulates endemically in Australia, frequently causing outbreaks of polyarthritis. Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, has been shown to play an instrumental role in the pathogenesis of rheumatoid arthritis. Studies using a mouse model of RRV disease have found macrophages to play a key role in disease pathogenesis and clinical outcome. Given this, we hypothesise that MIF may play a role in RRV disease. Methods Using the RRV disease mouse model we subcutaneously infected mice with 104 pfu RRV. Mice were monitored for disease signs and weighed daily. The clinical signs of disease were determined by assessing grip strength and altered gait. Mice were then scarified and tissues collected to determine levels of RRV and MIF expression. Results Preliminary results indicate that there is a correlation between the regulation of MIF and RRV disease. Experiments are continuing to determine the role of additional cytokines commonly associated with MIF. Results will be confirmed using a MIF knock-out mouse and in vitro studies. Conclusion Results of this study suggest a role of MIF in RRV pathogenesis. Additionally MIF may provide a target for the development of antiviral pharmaceuticals.