Abstract
AbstractChickens suffering from avian flu caused by H5N1 influenza virus are destined to die within 2 days due to a systemic inflammatory response. Since HVJ infection (1,2) and influenza virus infection (3,4) cause infected cells to activate homologous serum complement, the systemic inflammatory response elicited could be attributed to the unlimited generation of C5a anaphylatoxin of the complement system, which is a causative peptide of serious inflammation. In monkeys inoculated with a lethal dose of LPS (4 mg/kg body weight), inhibition of C5a by an inhibitory peptide termed AcPepA (5) rescued these animals from serious septic shock which would have resulted in death within a day (6). Therefore, we tested whether AcPepA could also have a beneficial effect on chickens with bird flu. On another front, enhanced production of endothelin-1 (ET-1) and the activation of mast cells (MCs) have been implicated in granulocyte sequestration (7). An endothelin receptor derived antisense homology box peptide (8) designated ETR-P1/fl was shown to antagonize endothelin A receptor (ET-A receptor) (9) and reduce such inflammatory responses as endotoxin-shock (10) and hemorrhagic shock (11), thereby suppressing histamine release in the circulation (12). Thus, we also administered ETR-P1/fl to bird flu chickens expecting suppression of a systemic inflammatory response.
Highlights
AcPepA treatment of bird flu chickens had no beneficial effect, ETR-P1/fl administration rescued all chickens from the lethal inflammatory response (Table 1)
ET-1 release is involved in histamine liberation and subsequent secondary granulocyte accumulation through tissue-specific activation of ET-A receptors
The direct effect of ET-1 induction is mainly pulmonary neutrophil activation, mast cells (MCs)-associated secondary changes are important in intestinal granulocyte recruitment [13]
Summary
AcPepA treatment of bird flu chickens had no beneficial effect, ETR-P1/fl administration rescued all chickens from the lethal inflammatory response (Table 1). ET-1 release is involved in histamine liberation and subsequent secondary granulocyte accumulation through tissue-specific activation of ET-A receptors.
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