Anti-inflammatory therapy in type 1 diabetes.
Type 1 diabetes (T1D) is a multi-factorial, organ-specific autoimmune disease in genetically susceptible individuals, which is characterized by a selective and progressive loss of insulin-producing β-cells. Cells mediating innate as well as adaptive immunity infiltrate pancreatic islets, thereby generating an aberrant inflammatory process called insulitis that can be mirrored by a pathologic autoantibody production and autoreactive T-cells. In tight cooperation with infiltrating innate immune cells, which secrete high levels of pro-inflammatory cytokines like IL-1β, TNFα, and INFγ effector T-cells trigger the fatal destruction process of β-cells. There is ongoing discussion on the contribution of inflammation in T1D pathogenesis, ranging from a bystander reaction of autoimmunity to a dysregulation of immune responses that initiate inflammatory processes and thereby actively promoting β-cell death. Here, we review recent advances in anti-inflammatory interventions in T1D animal models and preclinical studies and discuss their mode of action as well as their capacity to interfere with T1D development.
Institute of Physiological Chemistry, Ulm University, Albert Einstein Allee 11, 89081, Ulm, Germany. bernd.baumann@uni-ulm.de
Bernd
B
Baumann
Heba H
HH
Salem
Bernhard O
BO
Boehm
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015551:Autoimmunity / Q000187:drug effects; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B