title: Differential priming effects of proinflammatory cytokines on human neutrophil oxidative burst in response to bacterial N-formyl peptides.
abstract: Cytokines such as tumor necrosis factor alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 8 (IL-8), IL-6, IL-1 alpha, and IL-1 beta produced during the immune and inflammatory responses to bacterial stimuli have been reported to interact with polymorphonuclear neutrophil (PMN) activities. However, contradictory findings on their direct and priming effects on the PMN oxidative burst, which is essential for bacterial killing, have been reported. We have used a flow cytometry method to study the effects of these cytokines on the oxidative burst of PMN in whole blood to avoid PMN activation related to isolation procedures. None of the cytokines tested directly activated the PMN oxidative burst, but they did have differential priming effects on the oxidative burst in response to bacterial N-formyl peptides. TNF, GM-CSF, and IL-8 strongly primed a subpopulation of PMN to produce H2O2 in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), while IL-1 alpha, IL-1 beta, and IL-6 failed to do so. Furthermore, the addition of TNF, GM-CSF, or IL-8 to whole blood increased the capacity of a subpopulation of PMN to bind N-formyl peptides, a phenomenon that could account, at least in part, for the strong H2O2 production in response to FMLP after priming by the cytokines. The size of the primed hyperresponsive subpopulation was greater after priming with TNF or GM-CSF than after priming with IL-8. However, GM-CSF, TNF, and IL-8 at suboptimal concentrations cooperated in the induction of a subpopulation hyperresponsive to FMLP. These results show that, of the various proinflammatory cytokines tested, TNF, GM-CSF, and IL-8 strongly prime the PMN oxidative burst in response to bacterial peptides in whole blood and suggest that these cytokines may play a critical role in bacterial killing in vivo.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U294 et Laboratoire d'Immunologie et d'Hématologie, CHU X. BICHAT, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Elbim
authors.forename: S
authors.initials: S
authors.lastname: Bailly
authors.forename: S
authors.initials: S
authors.lastname: Chollet-Martin
authors.forename: J
authors.initials: J
authors.lastname: Hakim
authors.forename: M A
authors.initials: MA
authors.lastname: Gougerot-Pocidalo
mesh_terms: D016207:Cytokines / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*
chemical_list: D016207:Cytokines; D007378:Interleukins; D009240:N-Formylmethionine Leucyl-Phenylalanine; C049813:N-formylmethionyl-leucyl-phenylalanyl-lysine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006861:Hydrogen Peroxide