Recombinant human IL-26 facilitates the innate immune response to endotoxin in the bronchoalveolar space of mice <i>in vivo</i>

<div><p>Interleukin (IL)-26 is released in response to bacterial endotoxin (LPS) in the bronchoalveolar space of humans <i>in vivo</i> and it may potentiate neutrophil chemotaxis by enhanced IL-26 receptor stimulation. However, the effects of extracellular IL-26 protein on the innate immune response in the lungs <i>in vivo</i> remain unknown. Here, we characterized these effects of IL-26 on a wide range of aspects of the innate immune response to LPS in different compartments of the lungs <i>in vivo</i> over time. We administrated recombinant human (rh) IL-26 protein in the bronchoalveolar space using intranasal instillation in a mouse <i>in vivo</i> model, with and without prior instillation of LPS. We verified gene expression of the IL-26 receptor complex in mouse lungs and observed that, after instillation of LPS, rhIL-26 increases the phosphorylation of STAT3, a signaling molecule of the IL-26 receptor complex. We also observed that rhIL-26 exerted additional stimulatory and inhibitory actions that are compartment- and time-dependent, resulting in alterations of cytokines, proteinases, tissue inflammation and the accumulation of innate effector cells. Without the prior instillation of LPS, rhIL-26 exerted time-dependent effects on total gelatinase activity but few other effects. Most important, after instillation of LPS, rhIL-26 cleared inflammatory cells from local tissue and increased the accumulation of innate effector cells in the bronchoalveolar space. Tentatively, rhIL-26 may facilitate the innate immune response towards the bronchoalveolar space <i>in vivo</i> and represents a potential target for therapy in lung disorders involving the innate immune response.</p>