title: Anti-cytokine therapies in T1D: Concepts and strategies.
abstract: Therapeutic targeting of proinflammatory cytokines is clinically beneficial in several autoimmune disorders. Several of these cytokines are directly implicated in the pathogenesis of type 1 diabetes, suggesting opportunities for design of clinical trials in type 1 diabetes that incorporate selective cytokine blockade as a component of preventative or interventional immunotherapy. The rationale and status of inhibitory therapy directed against IL-1, TNF, IL-12, IL-23, and IL-6 are discussed, towards a goal of using cytokine inhibition as a therapeutic platform to establish an in vivo milieu suitable for modulating the immune response in T1D.
authors.affiliation: Benaroya Research Institute, 1201 Ninth Av, Seattle, WA 98101 USA. Electronic address: nepom@benaroyaresearch.org.
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Nepom
authors.forename: Mario
authors.initials: M
authors.lastname: Ehlers
authors.forename: Thomas
authors.initials: T
authors.lastname: Mandrup-Poulsen
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007167:Immunotherapy; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000276:immunology; D053759:Interleukin-23 / Q000037:antagonists & inhibitors / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D007004:Hypoglycemic Agents; D007375:Interleukin-1; D018664:Interleukin-12; D053759:Interleukin-23; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors
keywords: Anti-inflammatory; Autoimmunity; DAMPs; IL-1 receptor accessory protein; IL-1 receptor antagonist; IL-1RA; IL-1RAcP; Immunotherapy; LPS; NOD; ROS; Regulatory T cells; T1D; T2D; TLR; TXNIP; Teff; Treg; damage/danger-associated molecular patterns; effector T cell(s); lipopolysaccharide; non-obese diabetic (mice); reactive oxygen species; regulatory T cell(s); thioredoxin inhibitory protein; toll-like receptor; type 1 diabetes; type 2 diabetes