Anti-inflammatory potential of pyocyanin in LPS-stimulated murine macrophages

Abstract

Context: Pyocyanin is a typical Pseudomonas aeruginosa virulence factor, a common Gram-negative rod responsible for a wide range of severe nosocomial infections. There is evidence indicating that pyocyanin has multiple biological activities, but little is known about anti-inflammatory properties.

Objective: This study investigated pyocyanin effect on nitric oxide and cytokine production in lipopolysaccharide (LPS)-activated murine peritoneal macrophages.

Materials and methods: Macrophages were incubated in the presence and absence of pyocyanin (1, 5, 10, 50, and 100 µM) with and without LPS (1 µg/mL). Nitric oxide production was determined by Griess reagent and tumor necrosis factor (TNF)-α and interleukin (IL)-1β production was assessed by enzyme-linked immunosorbent assay. In addition, pyocyanin effects on zymosan A-induced peritonitis in mice were evaluated.

Results: Pyocyanin (5 and 10 µM) decreased nitric oxide, TNF-α, and IL-1β production independent of macrophage death. On the other hand, in vivo, pyocyanin (5 mg/kg) was not able to affect leukocyte migration into the site of inflammation.

Discussion and conclusion: Thus, our findings suggest that pyocyanin exerts anti-inflammatory effects on murine peritoneal macrophages, downregulating nitric oxide, TNF-α, and IL-1β levels, which seems to be independent of cell migration. These effects may represent a mechanism of immune evasion; nevertheless more detailed studies should be performed to confirm this hypothesis.

Keywords:

• Inflammation
• natural phenazines
• Pseudomonas aeruginosa
• macrophages
• immune response

Disclosure statement

All authors declare no conflicts of interest.

Additional information

Funding

The authors would like to demonstrate gratitude to National Council for Scientific and Technological Development (CNPq) for financial support of this project [Universal Project – MCTI/CNPq; number: 14/2013] and CAPES/PROCAD-2013, grant number 2951/2014.