Influenza infection exacerbates disease symptoms in relapsing models of multiple sclerosis

Abstract

Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Most patients present with a relapsing-remitting form (RRMS), wherein they experience new or exacerbated neurologic symptoms known as relapses followed by periods of partial or complete recovery (remissions). Previous evidence suggest that upper-respiratory infection increases the risk of relapse, but the mechanisms are ill-defined. The aim of this study was to elucidate the effects of upper-respiratory viral infection on disease progression in three models of relapsing experimental autoimmune encephalomyelitis (REAE). Relapsing EAE was induced in SJL/J, C57BL/6J and NOD/SHILtJ mice. At the peak of disease, mice were randomized into treatment groups, then inoculated with saline or mouse-adapted human influenza A virus (strain A/Puerto Rico/8/1934 H1N1; 0.7 HAU) two days later. Weights and scores were recorded daily. At day 42 post induction mice were euthanized and antigen recall responses measured from lymphocytes isolated from the spleen and cervical lymph nodes. Infection exacerbated symptoms of disease in both SJL/J and NOD/SHILtJ and tended to exacerbate disease in C57BL/6 mice. Following antigen stimulation, splenocytes and cervical lymph node lymphocytes from infected mice had increased production of IFNγ compared to cells isolated from saline inoculated controls. There was no effect of infection on IL-17A or GM-CSF production. These data indicate that infection may function to expand myelin-specific Th1 cell clones by an undefined mechanism. Together, these findings indicate influenza infection can exacerbate symptoms of REAE in SJL/J and NOD/SHILtJ mice.