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.

Background-In the host defence of the lung neutrophils (PMN) play a central role. Apart from antimicrobial properties, recent data indicate that PMN also exert anti-inflammatory eVects by stimulation and release of cytokine antagonists such as interleukin-1 receptor antagonist (IL-1ra). Methods-Cytokine release from lipopolysaccharide stimulated whole blood was studied in 18 patients with community acquired pneumonia (CAP) and severe co-morbidities at admission and after 24 hours. Release of IL-1ra, interleukin-1 (IL-1 ), tumour necrosis factor (TNF ), soluble TNF receptor type I (sTNF-RI), and IL-8 was determined by ELISA. Results-The mean (SD) leucocyte level at admission was 12.5 (4.1)/nl. There was a significant correlation between the release of anti-inflammatory cytokines such as IL-1ra and sTNF-RI and the leucocyte count at admission and after 24 hours. Additional in vitro experiments showed that co-incubation of peripheral blood mononuclear cells with autologous PMN led to a marked dose dependent increase in IL-1ra and sTNF-RI release. Conclusion-These results indicate that PMN may be responsible for the increase in anti-inflammatory cytokines in CAP. Strategies to increase neutrophil counts may exert beneficial eVects, not only by augmenting the antimicrobial activity but also by modulating the inflammatory cytokine response. (Thorax 2001;56:121-125)