Immunomodulatory effects of azithromycin on serum amyloid A production in lipopolysaccharide-induced endotoxemia in mice

Growing number of scientific investigations indicate that certain macrolides, a well-known group of antibiotics isolated from actinomycetes, also exert anti-inflammatory and immunomodulatory properties by modulating leukocyte function and circulating concentrations of proinflammatory cytokines. These macrolide properties have been employed in various chronic inflammatory disorders, such as diffuse panbronchiolitis, chronic obstructive pulmonary disease and cystic fibrosis.^{1, 2}

Recently, azithromycin (AZI), clarithromycin and telithromycin were shown to inhibit acute inflammatory processes in a murine model of lipopolysaccharide (LPS)-induced sepsis.^{3, 4, 5} The pathogenesis of sepsis involves a progressive and dynamic expansion of the systemic inflammatory response to bacterial infection.⁶ A major factor contributing to sepsis is the shedding of LPS from the cell wall of Gram-negative bacteria into the circulation. In response to infection and inflammatory stimuli, hepatocytes produce serum amyloid A (SAA) protein, which represents a family of low-molecular-weight acute-phase proteins.⁷ The main stimuli to the synthesis of SAA by the liver are cytokines, such as interleukin (IL)-6, IL-1β and tumor necrosis factor-α.⁸

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