Master regulator of intestinal disease: IL-6 in chronic inflammation and cancer development.
IL-6 signaling is of central importance for the maintenance of chronic intestinal inflammation in inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. IL-6 regulates T cell differentiation, activation and resistance against apoptosis and thereby controls the balance between pro-inflammatory T cell subsets such as Th1 or Th17 cells and immunosuppressive regulatory T cells. Furthermore, IL-6 has been implicated in the pathogenesis of colorectal cancer (CRC). In fact, IL-6 directly promotes tumor cell proliferation and survival through STAT3 activation. Due to its role in both types of diseases, IL-6 has been proposed as a missing link between inflammation and tumor development. During recent years, several therapeutics targeting IL-6 dependent pathways have been developed. Although clinical data about anti-IL-6 treatment in intestinal diseases are currently scarce, targeting this pathway might be a promising strategy in IBD and CRC.
Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.
Maximilian J
MJ
Waldner
Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany. Electronic address: markus.neurath@uk-erlangen.de.
Markus F
MF
Neurath
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D015850:Interleukin-6; D050796:STAT3 Transcription Factor
Colorectal cancer; Crohn's disease; Cytokines; Inflammatory bowel disease; Interleukin-6; JAK; SOCS3; STAT3; Ulcerative colitis