Effects of interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) on neutrophil elastase release.
The proinflammatory cytokine interleukin-6 (IL-6) and its potential opponent, transforming growth factor-beta (TGF-beta 1), have been discussed as being involved in the regulation of inflammatory processes following trauma and infections. The aim of this study was to investigate the effect of these cytokines on the regulation of neutrophil degranulation. The posttraumatic time courses of the plasma concentrations of IL-6, and the elastase-alpha 1-proteinase-inhibitor complex as marker of degranulation in patients undergoing severe trauma were found to be highly correlated, whereas TGF-beta 1 levels were determined to be not significantly altered. The close temporal correlation of IL-6 and elastase levels could be confirmed by investigation of exudates derived from the surgical area. To prove these in vivo findings, the effect of IL-6 and TGF-beta 1 on the degranulation of isolated neutrophils of healthy donors was investigated in vitro. Pathological high IL-6 concentrations were found to be capable of inducing a significant release of lysosomal elastase in a concentration-dependent manner, whereas the degranulation was unaffected by TGF-beta 1. In conclusion, these data suggest an involvement of IL-6 in the regulation of neutrophil degranulation under pathological conditions. However, TGF-beta 1 seems to have no direct regulatory effects besides its described chemotactic function on neutrophils.
Bank
U
U
Division of Experimental Internal Medicine, Otto von Guericke University Magdeburg, Medical School, Germany.
Reinhold
D
D
Kunz
D
D
Schulz
H U
HU
Schneemilch
C
C
Brandt
W
W
Ansorge
S
S
D015550:Cell Degranulation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D019272:Leukocyte Elastase / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D010196:Pancreatic Elastase / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014947:Wounds and Injuries / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D010450:Endopeptidases; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase