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Polymorphonuclear leucocytes selectively produce anti‐inflammatory interleukin‐1 receptor antagonist and chemokines, but fail to produce pro‐inflammatory mediators
Author(s) -
Schröder Anja K.,
Von Der Ohe Maren,
Kolling Ute,
Altstaedt Julia,
Uciechowski Peter,
Fleischer Daniela,
Dalhoff Klaus,
Ju XinSheng,
Zenke Martin,
Heussen Nicole,
Rink Lothar
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02435.x
Subject(s) - chemokine , cytokine , immunology , receptor antagonist , tumor necrosis factor alpha , peripheral blood mononuclear cell , macrophage inflammatory protein , interleukin 1 receptor antagonist , immune system , inflammation , macrophage , interleukin , biology , receptor , in vitro , antagonist , biochemistry
Summary The role of neutrophils in the immune response has long been regarded as mainly phagocytic, but recent publications have indicated the production of several cytokines by polymorphonuclear leucocytes (PMN). The results of the individual reports, however, vary considerably. In this study, we established a cytokine profile of pure human neutrophils and demonstrated that minor contamination of peripheral blood mononuclear cells (PBMCs) in PMN preparations can lead to false‐positive results. In our hands, peripheral blood PMN fail to produce the pro‐inflammatory cytokines interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐α (TNF‐α). Instead, they secrete large amounts of the chemokine IL‐8 and the anti‐inflammatory IL‐1 receptor antagonist (IL‐1ra). Additionally, PMN preparations of a high purity show production of the chemokines macrophage inflammatory protein (MIP)‐1α, MIP‐1β and growth‐related oncogene‐α (GRO‐α), as well as macrophage colony‐stimulating factor (M‐CSF). The neutrophil therefore represents a novelty by producing the antagonist of IL‐1β (i.e. IL‐1ra) in the absence of IL‐1β itself. To support our results, we differentiated stem cells from human cord blood into PMN and monocytes, respectively. These in vitro ‐differentiated PMN showed the same cytokine profile as peripheral blood PMN lacking IL‐1β, while differentiated monocytes produced the expected IL‐1β in addition to IL‐1ra. The clear anti‐inflammatory nature of their cytokine profile enables PMN to antagonize pro‐inflammatory signals in experimental conditions. It is therefore possible that PMN play a key role in immune regulation by counteracting a dysregulation of the inflammatory process. Clinical studies, in which administration of recombinant G‐CSF had a favourable effect on the outcome of severe infections and even sepsis without worsening inflammation, could thus be explained by our results.