In CF patients, S. aureus predominates in the lung of children and teenagers, while P. aeruginosa prevails in adults. Exopolysaccharide-enriched biofilms produced by P. aeruginosa increase the mucus viscosity, resistance to antibiotics and host immune effectors. Chronic bacterial infections are common in CF patients and facilitates lung inflammation, mucous obstruction and tissue remodeling, resulting in fatal loss of function. CF lungs display excessive inflammatory response, especially with increased neutrophil recruitment, the mechanism of this phenomenon is not adequately explained. However, intervention in this process likely will benefit CF patients. The role of the pro-inflammatory signaling cytokine Interleukin 1b in CF lung disease has been reported before. P. aeruginosa induces IL-1b or IL-18 production through NLRC4 inflammasome activation. P. aeruginosa flagellin and highly acylated LPS is recognized by TLR5 and TLR4 respectively. Human polymorphisms observed in the IL1B gene were associated with CF disease. CFTR deficient mice were found to be more susceptible to acute and chronic P. aeruginosa infection and display an exacerbated inflammatory response to LPS and P. aeruginosa activated alveolar macrophages from F508del mutant mice have enhanced expression of IL-1b. Huaux et al recently showed a deregulated inflammatory and fibrotic response in F508del mutant mice to bleomycin, which is IL-1R1 signaling dependent. Here we revisited the role of IL-1b in the resolution of P. aeruginosa infection, in a murine model based on mice carrying the most common CF mutation F508del CFTR. In this study, we show that excessive activation of IL-1b correlates with increased bacterial load, Epoxomicin inflammation and lung damage in F508del CFTR mice. Further, we show that IL-1b antibody neutralization attenuates the inflammatory response to P. aeruginosa infection. CF patients display increased susceptibility to chronic infections with opportunistic bacteria, excessive lung inflammation and fibrosis leading to fatal loss of function eventually. P. aeruginosa has been shown to induce IL-1b through NLRC4 inflammasome activation. CFTR deficient mice were found to be more susceptible to P. aeruginosa infection and have an exacerbated inflammatory response to LPS and P. aeruginosa. Furthermore, F508del CFTR mutant alveolar macrophages display an enhanced IL-1b production in response to LPS stimulation. Thus, we were interested in clarifying the role of IL-1b in the resolution of P. aeruginosa infection, in a murine model with the most common CF mutation F508del CFTR. Here, we show that, after P. aeruginosa infection, excessive activation of IL-1b in F508del CFTR mice compared to WT was accompanied by increased CFU in BALF, inflammation and lung damage. Further we show that a therapeutic antibody administration attenuates inflammatory response in an acute model of infection using WT mice. In CF patients bacterial infections persist and their chronicity facilitates lung inflammation, and subsequent tissue remodeling with severe loss of function.