Background Enterovirus 71 (EV71) is the commonest global cause of sporadic encephalitis. The encephalitis is associated with fatal cardiopulmonary collapse. There is no effective treatment. Pathophysiology is poorly understood.

Aim To explore the relationship between cytokine responses in cerebral and vascular compartments and patient outcome.

Methods Thirty cytokines were measured in cerebrospinal fluid (CSF) and sera from 85 Malaysians with EV71 infection, exhibiting either uncomplicated illness (n=45), meningitis (n=8), encephalitis (n=27) or encephalitis with cardiopulmonary collapse (n=6). Four of the latter patients died.

Results Patients who later required cardiac support had significantly raised concentrations of G-CSF, Interleukin-1β (IL-1β) and IL-1 receptor antagonist in the CSF and sera at admission (p=0.0005; p=0.004; p=0.029 respectively for sera). Sera cytokine levels were significantly associated with death (p=0.04). Combining the sera G-CSF:IL-5 ratio with clinical features at admission accurately predicted fatality (Sensitivity 100%, Specificity 96%).

Conclusion Cytokine responses in the vascular compartment predicted fatal outcome during EV71 infection. Il-1β has a negative inotropic action on the heart. Il-1 receptor antagonist (antagonist to IL-1β) and G-CSF are currently being assessed as treatments for acute cardiac impairment. The findings suggest we have identified functional markers of EV71 related cardiac dysfunction and potential treatments.