Longitudinal studies of inter-alpha inhibitor proteins in severely septic patients: a potential clinical marker and mediator of severe sepsis.
OBJECTIVE
To determine the clinical relevance and prognostic significance of serial measurement of inter-alpha inhibitor proteins (IalphaIp) in severely septic patients.


METHODS
A laboratory-based study of serial plasma samples over the first 5 days of severe sepsis from a prospective clinical trial.


METHODS
Small business and academic medical center research laboratories.


METHODS
Two hundred sixty-six patients with severe sepsis from a multiple-center phase III clinical trial.


METHODS
None.


RESULTS
Inter-alpha inhibitor proteins serve as endogenous serine protease inhibitors in human plasma. The levels of IalphaIp were markedly reduced to a mean value of 290+/-15 microg/mL at the onset of severe sepsis compared with normal plasma levels (617+/-197 microg/mL). Failure of IalphaIp levels to recover over the first 5 days of sepsis was associated with an unfavorable outcome (p<.001). IalphaIp levels were inversely correlated with interleukin-6 levels at study entry and over the first 5 days of management of severe sepsis. IalphaIp levels were significantly lower in women, with increased age, in the presence of multiple organ failure and in patients with intra-abdominal sources of sepsis.


CONCLUSIONS
Inter-alpha inhibitor proteins are markedly reduced in severe sepsis, and failure of recovery of IalphaIp levels over the course of sepsis is associated with an unfavorable outcome.
Opal
Steven M
SM
Infectious Disease Division, Brown Medical School, ProThera Biologics, LLC, East Providence, RI, USA.
Lim
Yow-Pin
YP
Siryaporn
Edward
E
Moldawer
Lyle L
LL
Pribble
John P
JP
Palardy
John E
JE
Souza
Sonia
S
D000328:Adult; D000510:Alpha-Globulins / Q000032:analysis*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000097:blood*; D012720:Severity of Illness Index; D013997:Time Factors
D000510:Alpha-Globulins; D015415:Biomarkers; C011877:inter-alpha-inhibitor