Title:Physiologic Versus Diabetogenic Effects of Interleukin-1: A Question of Weight
Volume: 20
Issue: 29
Author(s): Hugo O. Besedovsky and Adriana del Rey
Affiliation:
Keywords:
IL-1, physiologic functions, glucose homeostasis, inflammasome, IL-1 receptor antagonist, diabetes.
Abstract: Pleiotropic effects, great potency, and the capacity to induce its own production are distinguishing characteristics of IL-1.
Among the multiple physiological effects of this cytokine, we emphasize here its role in supporting immune processes by stimulating
most immune cells, and in re-setting glucose homeostasis. These aspects are complementary because stimulatory actions of IL-1 may be
due to its capacity to increase glucose uptake by immune cells in the periphery and to affect the control of glucose homeostasis at brain
levels, so as to deviate this main fuel to immune cells during inflammatory and infectious diseases. Thus, IL-1 can contribute to maintain
a lean phenotype, inhibit food intake, and exert hypoglycemic effects. However, these effects of IL-1 can be overridden particularly when
it is overproduced ectopically in other tissues, as it occurs during the autoimmune process that destroys the pancreas and causes type 1
diabetes, or when obesity triggers its production in adipose tissue and influences the development of type 2 diabetes. During obesity,
products of enlarged adipocytes, e.g. fatty acids, are sensed as danger signals by infiltrating immune cells and, together with hypoxia, results
in an ectopic overproduction of IL-1 that is largely mediated by activation of the NLRP3-caspase-1 inflammasome. Insulin and
leptin resistance develops by mutual IL-1β-TNFα induction, and hyperglycemia causes ectopic production of IL-1 in the pancreas, which
deregulates insulin production and favors the development of type 2 diabetes. In conclusion, whether IL-1 exerts physiologic or pathologic
effects depends on its amount and on the spatial and temporal pattern of its production.