Interleukin-6 potentiates neutrophil priming with platelet-activating factor
W. L. Biffl, E. E. Moore, F. A. Moore, V. S. Carl, F. J. Kim and R. J. Franciose
Department of Surgery, Denver General Hospital, University of Colorado Health Sciences Center.
BACKGROUND: Polymorphonuclear neutrophil (PMN) priming appears to be an
important event in the pathogenesis of hyperinflammatory states, resulting
in adult respiratory distress syndrome or multiple organ failure.
Interleukin-6 (IL-6) is an integral mediator of the acute stress response
to injury and infection, but excessive and prolonged systemic levels have
been associated with morbidity and mortality following trauma, burns, and
elective surgery. We hypothesized that IL-6 primed PMNs for exaggerated
cytotoxicity. However, we have been unable to directly prime PMNs for
superoxide release with IL-6. OBJECTIVE: To determine whether IL-6 acted in
concert with another inflammatory mediator (platelet-activating factor
[PAF]) to prime PMNs. METHODS: Polymorphonuclear neutrophils isolated from
healthy human donors were incubated for varying times with IL-6 (0.01 to
100 ng/mL), PAF (0.01 to 100 ng/mL), or a combination of IL-6 and PAF.
Superoxide production was then measured with and without the addition of
the PMN-activating formylpeptide formyl-methionyleucylphenylalanine.
RESULTS: Over the range of times (5 to 90 minutes) and doses tested, IL-6
did not prime PMNs, while PAF primed PMNs in a dose- and time-dependent
manner. Interleukin 6 (10 ng/mL) combined with a nonpriming concentration
of PAF (0.1 ng/mL) primed PMNs for superoxide production over a range of
incubation times. CONCLUSION: The inflammatory mediators IL-6 and PAF act
synergistically to prime PMNs in vitro. This observation may begin to
elucidate the mechanistic role of IL-6 in pathologic clinical states.
