Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease
M. Gardinali, P. Padalino, S. Vesconi, A. Calcagno, S. Ciappellano, L. Conciato, O. Chiara, A. Agostoni and A. Nespoli
University of Milan, Italy.
Complement activation is necessary for an adequate immune and inflammatory
response to infections. Activation releases anaphylatoxins that cause
vasodilation, increase vascular permeability, and trigger release of
polymorphonuclear neutrophil leukocyte (PMN) lysosomal enzyme and oxygen
radicals. Under normal circumstances, an orderly progression of such events
has a beneficial antimicrobial effect. The same mechanism, however, when
uncontrolled, may damage host tissues. To provide information about the
clinical importance of such events in sepsis, different complement
parameters (C3, C4, and the desarginated forms of C3a [C3a(des)-Arg] and
C5a [C5a(des)-Arg]), PMN elastase, and malondialdehyde (a by-product of
membrane peroxidation by oxygen radicals) were measured daily in 26 septic
patients and correlated with two objectively assessed and previously
validated severity scores (acute physiology and chronic health evaluation
[APACHE II] and Sepsis Severity Score [SSS]). Nonsurvivors (n = 12) had
significantly greater and longer lasting complement activation than that in
survivors, as reflected by higher levels of catabolic peptides
(C3a(des)-Arg) and lower levels of native proteins (C3 and C4).
C3a(des)-Arg, C3, C4, and the C3a(des)-Arg-C3 ratio were correlated with
Sepsis Severity Scores. Polymorphonuclear neutrophil leukocyte elastase
levels were higher in nonsurvivors and were correlated with C3a(des)-Arg
and the C3a(des)-Arg-C3 ratio. Malondialdehyde levels were significantly
higher in all patients than in controls, without, however, any relationship
to severity of disease or clinical outcome. Since the higher and more
persistent the complement activation and polymorphonuclear neutrophil
leukocyte stimulation, the worse the patient's prognosis, we conclude that
these mechanisms may be important in the clinical development of sepsis.
