Expression of Th2 Cytokines Decreases the Development of and Improves Behçet's Disease–Like Symptoms Induced by Herpes Simplex Virus in Mice

Abstract

In the etiology of Behçet's disease (BD), viral infection has long been postulated as a contributing factor, and viral involvement has been demonstrated. However, viral infection alone is not sufficient to explain the pathogenesis of BD, and some evidence suggests that immunologic abnormalities are also important. To study the possible role of immune regulation in the development of BD-like symptoms induced by herpes simplex virus inoculation in ICR mice, macrophages were deleted by use of liposome-encapsulated clodronate (lip-Cl(2)MDP). Treatment with lip-Cl(2)MDP suppressed the development of BD-like symptoms, and this suppression was correlated with the induction of interleukin-4 expression in mouse spleens. When the Th2 adjuvant ovalbumin (OVA)-alum was injected into mice with BD-like symptoms, their cutaneous symptoms improved. Adoptive transfer with splenocytes from OVA-alum-injected mice also resulted in improvement. These findings suggest that up-regulated Th2 cytokine expression can attenuate the development of and improve some BD-like symptoms.

The correlation of MHC haplotype and development of Behçet's disease-like symptoms induced by herpes simplex virus in several inbred mouse strains

“…The lower incidence of Behçet's diseaselike symptoms in Balb/c mice might be related to the production of higher IL-10 level and lower IFN-g level, contrary the higher incidence in C57BL/6 is dependent on higher IFN-g level and lower IL-10 level. This result matched our previous experiment that Th1/Th2 cytokine expression could regulate the development and attenuation of Behcet's disease-like symptoms in ICR mice [35].…”

Behcet’s disease

“…Thus, Th2 cytokine expression may be involved in attenuation of the symptoms of BD. In accordance with our findings, it was reported that depletion of macrophages suppressed BD-like symptoms and the suppression was correlated with IL-4 expression in splenocytes in the BD model of ICR mice [35]. Taken together, it is possible that the Th1 shift first occurred in BD via Txk overexpression in CD4+ T cells and Th2 cytokine production was modified to attenuate the inflammatory conditions.…”

Galectin-9 ameliorates herpes simplex virus-induced inflammation through apoptosis

“…It was later shown to also be expressed on Th17 cells (Hastings et al 2009). A strong Th1 immune response occurs in active BD and contributes to the prolonged inflammatory condition of BD (Frassanito et al 1999;Sohn et al 2001). Recently, highly expressed Th17 was also found to be related to inflammation in BD-like mice (Shim et al 2009).…”