Distribution of IL-1β immunoreactive cells in pancreatic biopsies from living volunteers with new-onset type 1 diabetes: comparison with donors without diabetes and with longer duration of disease
Although IL-1β is considered a key mediator of beta cell destruction, its cellular expression in islets during early type 1 diabetes remains unclear. We compared its expression in rare pancreatic biopsies from new-onset living volunteers with its expression in cadaveric pancreas sections from non-diabetic autoantibody-positive and -negative individuals and those with long-standing disease.
Pancreatic biopsy sections from six new-onset living volunteers (group 1) and cadaveric sections from 13 non-diabetic autoantibody-negative donors (group 2), four non-diabetic autoantibody-positive donors (group 3) and nine donors with diabetes of longer duration (0.25–12 years of disease; group 4) were triple-immunostained for IL-1β, insulin and glucagon. Intra- and peri-islet IL-1β-positive cells in insulin-positive and -negative islets and in random exocrine fields were enumerated.
The mean number of IL-1β-positive cells per islet from each donor in peri- and intra-islet regions was <1.25 and <0.5, respectively. In all study groups, the percentage of islets with IL-1β cells in peri- and/or intra-islet regions was highly variable and ranged from 4.48% to 17.59% in group 1, 1.42% to 44.26% in group 2, 7.93% to 17.53% in group 3 and 3.85% to 42.86% in group 4, except in a single case where the value was 75%. In 25/32 donors, a higher percentage of islets showed IL-1β-positive cells in peri-islet than in intra-islet regions. In sections from diabetic donors (groups 1 and 4), a higher mean number of IL-1β-positive cells occurred in insulin-positive islets than in insulin-negative islets. In group 2, 70–90% of islets in 3/13 sections had weak-to-moderate IL-1β staining in alpha cells but staining was virtually absent or substantially reduced in the remaining groups. The mean number of exocrine IL-1β-positive cells in group 1 was lower than in the other groups.
At onset of type 1 diabetes, the low number of islet-associated IL-1β-positive cells may be insufficient to elicit beta cell destruction. The variable expression in alpha cells in groups 2–4 suggests their cellular heterogeneity and probable physiological role. The significance of a higher but variable number of exocrine IL-1β-positive cells seen in non-diabetic individuals and those with long-term type 1 diabetes remains unclear.
KeywordsCytokines Immunohistochemistry Interleukin-1β Islet cells New-onset type 1 diabetes
Diabetes Virus Detection study
Mitogen-activated protein kinase
Network for Pancreatic Organ Donors with Diabetes
We thank Cell Signaling Technology for the supply of THP-1 cells with and without exposure to LPS, for use as immunohistochemical controls. From the Faculty of Medical and Health Sciences, University of Auckland (Auckland, New Zealand), we thank P. Browett for ongoing encouragement, D. van der Werf for statistical advice and J. Chong and A. Lim for checking the manuscript and preparing and revising the final version of tables. We thank the DiViD study for supplying rare pancreatic tail sections following biopsy from living donors newly-diagnosed with type 1 diabetes and A. Pugliese, I Kusmartseva and their team from nPOD for ready advice and supply of valuable cadaveric pancreatic sections with anonymous donor clinical characteristics. A brief report based on some of our findings was presented at the 2015 7th nPOD Scientific Meeting, St Pete Beach, FL, USA, and the Annual Scientific Meeting of the New Zealand Society for the Study of Diabetes, New Zealand, held in 2016 and 2017.
SR conceived and designed the experimental studies, carried out a considerable portion of them, acquired and analysed the data, wrote and revised the manuscript critically for publication and led and directed the study. FW, LK and KD-J made significant contribution to the conception of the study and its design and data interpretation. They also assisted in critically reading and offering valuable advice in revising the manuscript for intellectual content. CM, RH, JC and HW assisted in designing the studies, performed part of the experimental studies, acquired multiple microscopic images from several samples, carried out further data analysis and read and revised the relevant parts of the manuscript for scientific content. In addition, following discussions with SR, CM prepared all figures and carried out careful statistical analysis. All authors have given their final approval of the version to be published. SR is the guarantor of the work.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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