Endotoxin-induced release of the Th17-associated cytokine interleukin (IL)-26 in human neutrophils

Rationale: Neutrophils constitute key effector cells in host defense and may together with Th17 cells play an important role in chronic inflammatory disorders in the lungs, including asthma and COPD. Thus, the actions of neutrophils are likely to be of pathogenic significance. Moreover IL-26 is involved in the innate immune response to bacterial endotoxin in the airways of healthy human subjects. Here, the local concentrations of IL-26 correlate with those of neutrophils but it remains unknown to what extent neutrophils produce IL-26. Hypothesis: Neutrophils can produce IL-26 in response to bacterial and pro-inflammatory stimuli. Methods: Neutrophils were isolated from whole blood of healthy human volunteers. These neutrophils were then seeded ex vivo in culture media (10% FCS) and stimulated (18 h) with sub-maximally effective concentrations of endotoxin (from E. coli, 100 ng/ml), N-Formylmethionine-leucyl-phenylalanine (FMLP) (10µM) or IL-17A (100ng/ml). Cell-free conditioned media were collected and IL-26 protein concentrations quantified by ELISA. Results: We found that blood neutrophils release substantial amounts of IL-26 protein in response to endotoxin. However, neither FMLP nor IL-17A had any effects on IL-26 release. Conclusions: Human blood neutrophils can produce IL-26 protein in response to a stimulus from gram-negative bacteria. Given the recently proven involvement of both neutrophils and IL-26 in extra-pulmonary chronic inflammatory disorders in humans, our novel data forwards a solid rationale for further exploration of the pathogenic involvement of neutrophils and IL-26 in chronic inflammatory disorders in the lungs.