Modulation of virus-induced innate immunity and type 1 diabetes by IL-1 blockade
被引:20
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作者:
Hara, Naoko
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Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USAUniv Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA
Hara, Naoko
[1
]
Alkanani, Aimon K.
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Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USAUniv Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA
Alkanani, Aimon K.
[1
]
Dinarello, Charles A.
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Univ Colorado, Sch Med, Div Infect Dis, Aurora, CO USAUniv Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA
Dinarello, Charles A.
[2
]
Zipris, Danny
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Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USAUniv Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA
Zipris, Danny
[1
]
机构:
[1] Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA
[2] Univ Colorado, Sch Med, Div Infect Dis, Aurora, CO USA
We used the LEW1.WR1 model of Kilham rat virus (KRV)-induced type 1 diabetes (T1D) to test the hypothesis that blocking IL-1 pathways early in the course of the disease can modulate virus-induced innate immunity and prevent disease progression. Administering KRV plus IL-1 receptor antagonist (Anakinra) for 14d prevented insulitis and T1D. Anakinra reversed the KRV-induced systemic inflammation evidenced by the accumulation of T cells in the spleen and pancreatic lymph nodes on d 5 post-infection. Blocking IL-1 modulated the level of IRF-7 and IL-6 gene expression in the spleen and the p40 subunit of IL-12 and IL-23 in the serum. Anakinra did not interfere with the ability of LEW1.WR1 rats to clear the virus from the spleen, pancreatic lymph nodes or serum. Consistent with these data, normal levels of KRV-specific adaptive immune responses were detected in in the spleen and peripheral blood of the treated animals. Finally, blocking IL-1 pathways reversed the KRV-induced modulation of gut bacterial communities. The data may imply that IL-1 pathways are directly linked with early mechanisms whereby KRV infection leads to islet destruction, raising the hypothesis that blocking IL-1 pathways early in the course of the disease could be a useful therapeutic approach for disease prevention.
机构:
Univ Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, Italy
Fdn Umberto Di Mario ONLUS, Siena, ItalyUniv Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, Italy
Spagnuolo, Isabella
Patti, Aurora
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Univ Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, Italy
Fdn Umberto Di Mario ONLUS, Siena, ItalyUniv Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, Italy
Patti, Aurora
Sebastiani, Guido
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Univ Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, Italy
Fdn Umberto Di Mario ONLUS, Siena, ItalyUniv Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, Italy
Sebastiani, Guido
Nigi, Laura
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Univ Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, ItalyUniv Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, Italy
Nigi, Laura
Dotta, Francesco
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Univ Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, Italy
Fdn Umberto Di Mario ONLUS, Siena, ItalyUniv Siena, Dept Med Surg & Neurosci, Diabet Unit, Siena, Italy
机构:
Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USAUniv Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA
机构:
Univ Colorado Denver, Dept Med, Aurora, CO USA
Radboud Univ Nijmegen, Med Ctr, Dept Med, Nijmegen, NetherlandsUniv Colorado Denver, Dept Med, Aurora, CO USA