Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.
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.
J H
JH
Stevens
P
P
O'Hanley
J M
JM
Shapiro
F G
FG
Mihm
P S
PS
Satoh
J A
JA
Collins
T A
TA
Raffin
D000818:Animals; D000906:Antibodies / Q000032:analysis*; D001794:Blood Pressure; D002449:Cell Aggregation; D003182:Complement C5 / Q000031:analogs & derivatives / Q000276:immunology*; D015936:Complement C5a; D015937:Complement C5a, des-Arginine; D006339:Heart Rate; D007962:Leukocytes / Q000166:cytology; D008252:Macaca fascicularis; D011669:Pulmonary Wedge Pressure; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000276:immunology*; D018805:Sepsis / Q000150:complications*; D014655:Vascular Resistance
D000906:Antibodies; D003182:Complement C5; D015937:Complement C5a, des-Arginine; D015936:Complement C5a