Monocyte dysfunction in severe trauma: evidence for the role of C5a in deactivation.

Consecutive severely traumatized patients (n = 16) requiring intensive care underwent serial monitoring of complement activation and monocyte migratory function with the chemoattractant activated serum (C5a) and formyl-methionyl-leucyl-phenylalanine (FMLP). Complement was found to be activated, and chemotaxis to C5a was correspondingly depressed maximally at a mean 5 to 7 days after injury (p = less than 0.01). The migratory response to FMLP was within the normal range throughout. Conversely, in a consecutive series of patients undergoing aortoiliac bypass grafting (n = 11), there was no evidence of complement activation, and monocyte migratory function remained normal for both C5a and FMLP. These data suggest that in patients with severe trauma, the activation of complement, particularly the fifth component (C5a), reduces the migratory responsiveness of circulating monocytes to C5a. This reduction in a host-response mechanism may explain the propensity to infection and poor wound healing seen in patients with severe trauma and also indicates that C5a, thought to be the major in vivo chemoattractant for leukocytes, has profound systemic actions.