Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates

J Clin Invest. 1986 Jun;77(6):1812-6. doi: 10.1172/JCI112506.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / analysis*
  • Blood Pressure
  • Cell Aggregation
  • Complement C5 / analogs & derivatives
  • Complement C5 / immunology*
  • Complement C5a
  • Complement C5a, des-Arginine
  • Heart Rate
  • Leukocytes / cytology
  • Macaca fascicularis
  • Pulmonary Wedge Pressure
  • Respiratory Distress Syndrome / complications
  • Respiratory Distress Syndrome / immunology*
  • Sepsis / complications*
  • Vascular Resistance

Substances

  • Antibodies
  • Complement C5
  • Complement C5a, des-Arginine
  • Complement C5a