Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 21 P147

Imperial College, London, UK.


Sepsis continues to be a leading clinical problem, with ~1.8 million people worldwide affected. This continual increase in sepsis and related deaths is in part due to age, increased frequency of invasive procedures and widespread bacterial antibiotic resistance, with mortality often related to underlying disorders that often accompany sepsis. Sepsis affects the brain, and the impairment of brain function is often associated with severe infectious disease1. The endogenous anti-inflammatory protein Annexin 1 affords its protection via the FPR family2. Here we assessed whether Annexin 1 could protect against the cerebral inflammation associated with experimental endotoxaemia.

Adult male mice (C57BL/6) treated for 2 h with LPS (10 μg/mouse, i.p.) exhibited a decrease in rolling and an increase in adherent leukocytes in the cerebral microcirculation, as demonstrated using intravital microscopy. Following the administration of Annexin 1 N-terminus-derived peptide Ac2–26 (100 μg/mouse, i.v.), a significant decrease in the number of adherent leukocytes was observed. This effect was abrogated following the co-administration of the FPR antagonist Boc2, suggesting that the protective effect of Annexin 1 peptide Ac2–26 was mediated by a member(s) of FPR. Serum samples were taken and inflammatory cytokines were measured, e.g. tumor necrosis alpha (TNFα) and IL-1β. LPS caused an increase in these inflammatory cytokines, which were suppressed following peptide Ac2–26 administration.

For the first time, these results demonstrate that the Annexin 1 peptide Ac2–26 affords cerebroprotection in experimental endotoxaemia and furthermore, these effects appear to mediated via an FPR-family mechanism.

References:

1. John CD, Gavins FN, Buss NA, Cover PO & Buckingham JC. Annexin A1 and the formyl peptide receptor family: neuroendocrine and metabolic aspects. Current Opinion in Pharmacology 2008 8 765–776.

2. Stocchetti N. Brain and sepsis: functional impairment, structural damage, and markers. Anesthesia and Analgesia 2005 101 1463–1464.

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