Modulation of cytokine responses by adrenomedullin and adrenomedullin binding protein-1 in macrophages: a novel pathway in sepsis.

نویسندگان

  • L Y F Wong
  • B M Y Cheung
چکیده

Polymicrobial sepsis is a life-threatening disorder. Patients die of septic shock and multiple organ failure caused by lipopolysaccharide (LPS) and other bacterial products. A hyperdynamic phase is followed by shock and circulatory collapse. Myocardial dysfunction frequently accompanies severe sepsis and septic shock secondary to circulating depressant factors, including tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Macrophages produce proinflammatory cytokines including TNF-α, IL-1β, and IL-6 that lead to tissue injury. Adrenomedullin (AM) is a vasorelaxant peptide originally isolated from the adrenal medulla. It relaxes vascular smooth muscle cells through the elevation of intracellular cyclic adenosine 3’-5’-monophosphate (cAMP).1 It also acts on endothelial cells by activating adenylyl cyclase and nitric oxide synthase, resulting in dilation of blood vessels. The macrophage produces AM in inflammation and sepsis. Transgenic mice overexpressing AM are resistant to septicaemic shock. AM markedly increased IL-6 production in both resting and LPS-stimulated macrophages, but significantly suppressed LPS-induced TNF-α secretion.2 IL-6 and IL-10 can inhibit the production of pro-inflammatory cytokines such as TNF-α and IL-1. These results suggest that AM may play an important role as an anti-inflammatory regulator Hong Kong Med J 2015;21(Suppl 4):S39-44 RFCID project number: 05050082 LYF Wong, BMY Cheung *

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عنوان ژورنال:
  • Hong Kong medical journal = Xianggang yi xue za zhi

دوره 21 Suppl 4  شماره 

صفحات  -

تاریخ انتشار 2015