Human herpesvirus 6 reactivation and inflammatory cytokine production in patients with drug-induced hypersensitivity syndrome

BackgroundHuman herpesvirus 6 (HHV-6) reactivation has been suggested to modify the clinical features of drug induced hypersensitivity syndrome (DIHS). However, mechanisms for viral reactivation and modification of the clinical features remain unclear.ObjectiveTo determine whether cytokines play an important role in viral reactivation and modification of the clinical features.Study DesignWe examined the kinetics of serum cytokines and viral load in HHV-6 infections of six patients with DIHS.ResultsHHV-6 infection occurred three to four weeks after the onset of disease. Elevated TNF-α and IL-6 levels were observed to precede HHV-6 infection in four of the six patients. Although high levels of IL-6 were observed in samples collected prior to HHV-6 infection, the amounts of this cytokine significantly decreased to undetectable levels during viral infection in five of the six patients. Subsequently, serum IL-6 levels were increased after viral infection in five patients. IL-1β levels were also increased at the time of viral infection in three of the six patients. Neither IL-4 nor IFN-γ could be detected in any of the samples.ConclusionThese results demonstrate that cytokines play an important role in HHV-6 reactivation in patients with DIHS.