Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Temporal changes in cytokine expression following coxsackievirus infection of human islets (#75)

Ammira Al-Shabeeb Akil 1 2 , Anand A Hardikar 3 , William D Rawlinson 1 4 5 , Maria Craig 1 2 6
  1. Virology Research, Prince of Wales Hospital Research Laboratories, South Eastern Area Laboratory Services, Prince of Wales Hospital, Sydney, Australia
  2. School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, Sydney, Australia
  3. NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, Australia
  4. School of Biotechnology and Biomolecular Science, Faculty of Science, University of New South Wales, Sydney, Australia
  5. School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia
  6. Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Sydney, Australia
Human enteroviruses, particularly the Coxsackievirus B (CVB) group, demonstrate β-cell tropism, and may initiate and/or accelerate type 1 diabetes (T1D). Circulating levels of multiple pro-inflammatory cytokines and chemokines are elevated before and at diagnosis of T1D, and contribute to β-cell death in vitro. Thus, we examined the cytokine response in human islets following CVB infection. Donor islets were infected with clinical strains of CVB3, 4 and 5 and the concentration of 50 human cytokines, chemokines and growth factors (using the Luminex-MagPix assay) was measured on day 1, 3, 5, 7 and 10 post infection. Nonparametric (Kruskall-Wallis and Mann-Whitney U) tests were used to compare the distribution of cytokines for all three viruses vs the no virus control (NVC), with significant results (p<0.05) reported. All CVBs infected and replicated in the islets, with CPE and β-cell death observed by day 10. On day 1 post infection, elevation of interleukin (IL)1β and IL7 was observed for all CVBs compared with the NVC. Interferon(IFN)α, chemokine ligand (CCL)8, CCL22, fibroblast growth factor (FGF)2 and epidermal growth factor (EGF) increased for CVB3 only, IL33 and CCL13 for CVB4 only; CCL17 and CCL27 for CVB5, while IL16 decreased for CVB4 and CVB5. On day 3, IL1β remained elevated for all three viruses, with increased levels of IFNα, IL33, FGF2 and EGF for CVB3; IL33 and EGF for CVB4; sCD40L and CCL27 for CVB5, with IL16 decreased for CVB4 and CVB5. On day 7 IFNα was significantly elevated for CVB3, and CCL1, CCL11, CCL13, CCL17, CCL27, IL16, IL33, and Thrombopoietin (TPO) for CVB5. In conclusion, distinct and time dependent cytokine, chemokine and growth factor profiles are observed following infection of human islets with CVBs, which differ from circulating cytokine responses. The strain specific effects on intracellular cytokine production and their potential effects on diabetogenicity warrant further investigation.