Therefore, we tested the effect of a therapeutic antibody against murine IL-1b in our acute P. aeruginosa infection model in WT mice. IL-1b neutralization has been successfully tested previously with this antibody in a model of intestinal inflammation. Twenty hours after P. aeruginosa infection, IL-1b antibody administration caused a decrease in the inflammatory parameters and in bacterial load, as compared with NaCl-treated mice. This is consistent with studies by Schultz et al. who showed that inhibition of the IL-1R1 pathway by either the IL1R1 mutation or application of the IL-1b antagonist IL-1RA improved antibacterial host defense and reduced CHIR-99021 pro-inflammatory cytokine production. Reduced neutrophil recruitment by IL-1b neutralization could be due to reduced endothelial activation. For instance, TNF-a and IL-17 synergize to induce in cultured endothelial cells the expression of P- and E-selectin, as well as neutrophil chemokines, increasing neutrophil transmigration. IL-1b produced by activated monocytes was shown to augment the expression of adhesion molecules in vitro. Thus, the diminished leucocyte recruitment we observe with IL-1b neutralization could be related to a reduced endothelial activation. Abnormal recruitment and metabolic adaptation of neutrophils in human CF airways has been demonstrated, the molecular mechanism remains to be established but likely involves IL-1b signaling based on the arguments mentioned above. We cannot exclude a role of lung fibroblasts and myoblasts. Indeed, IL-1b stimulated human cardiac fibroblasts overexpress adhesion molecules and neutrophil chemoattractant. In conclusion we propose that the IL-1b pathway is critical to drive excessive and detrimental inflammation in F508del mouse model of CF. We show here that antibody neutralization of IL-1b is well tolerated in mice, has no effect on the unchallenged lung in WT or F508del CFTR mice, whereas it can reduce pathology induced by acute bacterial lung infection. Systemic sclerosis is an autoimmune disease characterized by microvascular dysfunction, activation of the immune system and tissue fibrosis. Pathogenesis of SSc is complex and poorly understood and it has been suggested that a genetic predisposition might contribute to the development of the disease together with environmental agents, such as viruses or chemical agents, which could activate both cellular and humoral immunity. According to the current understanding, immune system leads to vascular injury with either release of proinflammatory cytokine or production of auto-antibodies that damage endothelial cells, resulting in promoted fibroblast proliferation. So far the contribution of complement system to the pathogenesis of SSc has not been deeply investigated, most likely because in clinical practice the main plasma complement proteins are usually within the reference range. Nevertheless, hypocomplementemia has been described in SSc patients with more severe disease, while high plasma levels of complement activation products have been correlated with clinical severity of SSc.