Chemokines as drug targets in type 1 diabetes.
Acute or chronic inflammation is thought to play a major role in the etiology and/or pathogenesis of autoimmune disease. Often viral infections are the initial cause for a local inflammatory reaction resulting in tissue infiltration by activated leukocytes. The activation and trafficking of these leukocytes to the site of inflammation is conducted by chemoattractant cytokines, termed chemokines. Depending on the genetic background and the history of previous infections, such infiltrating leukocytes can potentially include autoaggressive lymphocytes with specificity to tissue antigens. The number of specific precursor lymphocytes, strength of activation and degree of counteracting immunoregulatory measures determine whether such an autoimmune incident ultimately results in autoimmune disease. Thus, by blocking the initial inflammatory insult one could in theory prevent the excessive attraction of autoaggressive lymphocytes to the inflammation site and the subsequent formation of a pattern that leads to autoimmune disease. This review focuses on blocking of chemokines in animal models of type 1 diabetes and discusses the possible applications of such treatments in human autoimmune disease.
Christen
Urs
U
Pharmazentrum Frankfurt, Zentrum fur Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES), Johann Wolfgang Goethe University, Frankfurt am Main, Germany. christen@med.uni-frankfurt.de
D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology; D054357:Chemokine CXCL10; D018925:Chemokines / Q000502:physiology*; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology; D051379:Mice; D010179:Pancreas / Q000473:pathology
D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D007004:Hypoglycemic Agents