Interleukin-6 potentiates neutrophil priming with platelet-activating factor.
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.


CONCLUSIONS
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.
Department of Surgery, Denver General Hospital, University of Colorado Health Sciences Center.
W L
WL
Biffl
E E
EE
Moore
F A
FA
Moore
V S
VS
Carl
F J
FJ
Kim
R J
RJ
Franciose
D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology*; D011994:Recombinant Proteins; D012016:Reference Values; D013997:Time Factors
D015850:Interleukin-6; D010972:Platelet Activating Factor; D011994:Recombinant Proteins