IL-10 is pathogenic during the development of coxsackievirus B4-induced chronic pancreatitis.
Using a mouse model of coxsackievirus B4 (CVB4-V)-induced chronic pancreatitis, we investigated whether cytokines are involved in the progression of acute disease to chronic inflammatory disease. We show that IL-10 contributed to the development of chronic pancreatitis since acute disease resolved when IL-10 was absent or when IL-10 signaling was disrupted. We explored the underlying mechanisms by which IL-10 affected disease progression, using a novel approach to assess immunological events occurring in situ. Multiple markers that define functional innate immune responses and functional T cell responses were monitored over the course of CVB4-V infection of wild-type and IL-10 knockout mice, using a multiplex transcriptional profiling approach. We show that high levels of IL-10 early during infection were associated with delayed innate and T cell responses. Furthermore, high IL-10 production correlated with altered kinetics of T regulatory responses indicating a disruption in the balance between effector and regulatory T cell responses.
Gu
Rui
R
Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12208, USA.
Shampang
Anae
A
Reilly
Andrew
A
Fisher
Dusti
D
Glass
William
W
Ramsingh
Arlene I
AI
D000818:Animals; D003384:Coxsackievirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D029822:Enterovirus B, Human / Q000276:immunology / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D016753:Interleukin-10 / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000821:virology; D050500:Pancreatitis, Chronic / Q000209:etiology / Q000276:immunology* / Q000821:virology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
D016753:Interleukin-10