Overing one pseudomonad that shared this same hypersecretion phenotype. B. cepacia and A. xyloxidans appear to be “agmatine neutral” having no effect on agmatine concentrations in liquid culture. To determine if the lung could serve as a source of agmatine during infection we exposed mouse lungs to LPS and various P. aeruginosa mutants of agmatine metabolism and measured the agmatine found in bronchoalveolar lavage fluid by UPLCMS/MS. The BAL fluid demonstrates the presence of agmatine at baseline, increasing levels with LPS treatment, but dramatically higher levels with bacterial infection. To demonstrate that this mouse-derived agmatine could be detected by infecting bacteria the agmatine neutral Silmitasertib mutant was also engineered to contain an agmatine responsive bioluminescent reporter by fusing the promoter and beginning coding sequence of the aguBA operon into a single copy, genomically-integrated lux operon. This mutant produces light in a dose dependent fashion when exposed to extracellular agmatine whereas its “empty vector” control strain does not. The light output of the infecting mutant was measured and normalized to either the infecting inoculum at time zero or the recovered bacterial colony count from the BAL. The reporter demonstrates a significantly higher light output over the chest during pneumonia than does the vector control reporter that does not respond to agmatine. This demonstrates bacterial detection of host agmatine during lung infections. Combined, these experiments suggest that sputum agmatine concentrations could be derived from either the host lung or, in some instances, the bacteria themselves, and are subject to bacterial manipulation. As sputum from patients with cystic fibrosis represents a chronic infection, it is unlikely agmatine will act on naı ¨ve cells free of other co-stimulants. When the agmatine titration in macrophages was repeated with LPS co-stimulation, a reversal in effect with an inhibition of TNF-a in LPS stimulated cells was observed. This suggests agmatine is capable of both immune activation and inhibition dependent on dose, and the presence of co-stimulatory molecules. Furthermore, the effective dose range is within the true biologic range measured in sputum suggesting these immunomodulatory effects may occur within the more complex environment of the lung. To determine which of these effects occur within the multicellular environment of a mammal we utilized a mouse model of real time inflammation. The HLL mouse contains the gene for luciferase fused to an NF-kB response element. Thus cellular expression of NF-kB in a live animal can be monitored by luminescence output after administration of systemic luciferin using an animal imaging station. Agmatine was intratracheally injected into the lungs of these NF-kB reporter mice and luminescence over the lung field was measured revealing a significant increase in lung NF-kB expression at 24 hours compared to PBS injection alone.