Evidence for a crucial role of neutrophil-derived serine proteases in the inactivation of interleukin-6 at sites of inflammation

FEBS Lett. 1999 Nov 19;461(3):235-40. doi: 10.1016/s0014-5793(99)01466-0.


The bioactivity of interleukin-6 (IL-6) was found to be dramatically reduced in fluids from sites of inflammation. Here, we provide evidence that the neutrophil-derived serine proteases elastase, proteinase 3 and cathepsin G are mainly involved in its degradation and subsequent inactivation. The initially hydrolyzed peptide bonds were detected to be Val(11)-Ala(12) and Leu(19)-Thr(20) (elastase), Phe(78)-Asn(79) (cathepsin G) and Ala(145)-Ser(146) (proteinase 3). The soluble IL-6 receptor elicits a protective effect against the IL-6 inactivation by cathepsin G only. The inactivation of IL-6 by neutrophil-derived serine proteases might act as a feedback mechanism terminating the IL-6-induced activation of neutrophils.

Publication types

  • Comparative Study

MeSH terms

  • Cathepsin G
  • Cathepsins / physiology*
  • Exudates and Transudates / enzymology*
  • Exudates and Transudates / immunology
  • Feedback
  • Humans
  • Inflammation / enzymology*
  • Inflammation / immunology
  • Interleukin-6 / analysis
  • Interleukin-6 / antagonists & inhibitors*
  • Leukocyte Elastase / physiology*
  • Myeloblastin
  • Neutrophils / enzymology*
  • Serine Endopeptidases / physiology*


  • Interleukin-6
  • Cathepsins
  • Serine Endopeptidases
  • CTSG protein, human
  • Cathepsin G
  • Leukocyte Elastase
  • Myeloblastin