The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition.
Interleukin-6 has long been recognized as a prototypic pro-inflammatory cytokine that is involved in the pathogenesis of all inflammatory diseases. Activation of the gp130 homodimer by IL-6 leads to the initiation of Jak/STAT signaling, a pathway that is often constitutively switched on in inflammatory malignancies. However, a plethora of studies in the last decade has convincingly shown that only signaling via the soluble IL-6R (trans-signaling) accounts for the deleterious effects of IL-6, whereas classic signaling via the membrane-bound receptor is essential for the regenerative and anti-bacterial effects of IL-6 (classic signaling). In this review, we highlight recent developments in the field of IL-6 research, and specifically focus on advances towards a safe and specific inhibition of IL-6 trans-signaling.
Institute of Biochemistry, Kiel University, Olshausenstrasse 40, Kiel, Germany.
Christoph
C
Garbers
Institute of Biochemistry, Kiel University, Olshausenstrasse 40, Kiel, Germany.
Samadhi
S
Aparicio-Siegmund
Institute of Biochemistry, Kiel University, Olshausenstrasse 40, Kiel, Germany. Electronic address: rosejohn@biochem.uni-kiel.de.
Stefan
S
Rose-John
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C502936:tocilizumab