Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.
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| Abstract |
In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, control, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with anti-C5a antibodies did not die and did not develop decreased oxygenation (P less than 0.05) or increased extravascular lung water (P less than 0.05). They also had a marked recovery in their mean arterial blood pressure (P less than 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.
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| Authors | J H Stevens, P O'Hanley, J M Shapiro, F G Mihm, P S Satoh, J A Collins, T A Raffin |
| Journal | The Journal of clinical investigation (J Clin Invest) Vol. 77 Issue 6 Pg. 1812-6 (Jun 1986) ISSN: 0021-9738 [Print] United States |
| PMID | 3711336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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