Interleukin-6 delays neutrophil apoptosis.
BACKGROUND
Neutrophil (PMN) apoptosis promotes the phagocytosis of PMNs without inciting an inflammatory response or local cytotoxic effect. This is important in the normal resolution of inflammatory processes and the control of tissue injury. Conversely, a delay in PMN apoptosis may facilitate PMN-mediated organ dysfunction by extending PMN functional integrity at an inflammatory site. Elevated circulating and tissue levels of interleukin-6 (IL-6) have been associated with postinjury organ dysfunction, and IL-6 appears to augment PMN cytotoxic functions. Therefore, we hypothesized that IL-6 delays PMN apoptosis, thereby enhancing PMN-mediated cytotoxicity.


METHODS
Neutrophils isolated from healthy human donors were incubated for 24 hours in enriched RPMI 1640 cell culture medium at 37 degrees C in 5% carbon dioxide. Subgroups were incubated with IL-6, heat-denatured IL-6, or buffer alone. Apoptosis was assessed morphologically using acridine orange-ethidium bromide stain, and biochemically by DNA gel electrophoresis. Functional capacity of PMNs was assessed by superoxide generation after activation with phorbol myristate acetate or platelet-activating factor plus formyl-methionyl-leucyl-phenylalanine.


RESULTS
Treatment with IL-6 resulted in a greater population of surviving (nonapopototic) PMNs after 24 hours. In addition, the IL-6-treated population produced more superoxide after 24 hours than did the untreated or heat-denature IL-6-treated groups, after either activating stimulus.


CONCLUSIONS
Interleukin-6 delays PMN apoptosis, resulting in a larger population of surviving PMNs with a greater collective capacity for superoxide production. This could potentially facilitate PMN-mediated tissue injury and may be a mechanism whereby IL-6 contributes to organ dysfunction.
Department of Surgery, Denver General Hospital, USA.
W L
WL
Biffl
E E
EE
Moore
F A
FA
Moore
C C
CC
Barnett
V S
VS
Carl
V N
VN
Peterson
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism
D015850:Interleukin-6; D013481:Superoxides