High mobility group box 1 protein (HMGB1) is a ubiquitous nuclear protein that also acts as a Damage Associated Molecular Pattern (DAMP) and promotes inflammation when released outside the cell. HMGB1 is significantly elevated in CF sputum, and it is reported as a CF biomarker. Patients with high HMGB1 in broncho-alveolar lavage experience a significantly faster decline of lung function. Previous research showed that neutralizing HMGB1 with monoclonal antibodies conferred significant protection against P. aeruginosa infection, neutrophil recruitment and lung injury. Since the use of monoclonal antibodies in CF patients is expensive and impractical, these researchers embarked on a drug discovery project to find new HMGB1 inhibitors. So they identified a promising drug candidate, pamoic acid (PAM). PAM will be tested in comparison with neutralizing monoclonal antibodies to HMGB1 in established animals models of acute and chronic respiratory infection. The specific aim of the project is to prove that aerosol delivery of pamoic acid (PAM) can ameliorate neutrophilic inflammation and lung damage in wt and CF mice infected with P. aeruginosa.