TABLE 3

Does IL-6 play a role in β-cell destruction and apoptosis?

SettingFor an impact of IL-6 on β-cells (ref. no.)Against an impact of IL-6 on β-cells (ref. no.)
In vitroIL-6 alone is not cytotoxic to rat and human islets/β-cells (3135).
IL-6 potentiates IL-1–induced NO synthesis in rat islets (34).IL-6 does not potentiate cytokine-induced NO synthesis in human islets (33).
IL-6 and dexamethasone induces Reg gene expression in RIN-m5F cells (36).
IL-6 protects mouse pancreatic islets and β-cells from inflammatory cytokine-induced cell death and functional impairment both in vitro and in vivo (37).
In vivo human autopsiesThe HIP/PAP is expressed in islets of a new-onset type 1 diabetic patient and is released from healthy cadaveric human islets upon IL-6 treatment. HIP/PAP acts as a T-cell autoantigen in NOD mice (38).IL-6 islet expression does not correlate with insulitis/β-cell destruction in humans (35).
Rodent insulitisIL-6 islet expression correlates with insulitis/β-cell destruction in NOD mice (35), and islet IL-6 expression is higher in NOD females than in males (39).
Il6-Tg under the control of the insulin promoterβ-Cell–specific overexpression of Il6 promotes islet inflammation in the NOD mouse (40) and in a non–diabetes-prone mouse strain (41).IL-6 delays overt diabetes development in NOD mice (40) and the nondiabetic strain does not develop diabetes (41).
Il6-TgIl6-Tg non–diabetes-prone mice do not develop autoimmune diabetes (8).
Double Il6-Il6Rα-TgDouble Il6-Il6Rα-Tg non–diabetes-prone mice do not develop autoimmune diabetes (42).
  • HIP/PAP, hepatocarcinoma-intestine-pancreas/pancreatic-associated protein; Tg, transgenic.