title: Longitudinal studies of inter-alpha inhibitor proteins in severely septic patients: a potential clinical marker and mediator of severe sepsis.
abstract: 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.
authors.affiliation: Infectious Disease Division, Brown Medical School, ProThera Biologics, LLC, East Providence, RI, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Opal
authors.forename: Yow-Pin
authors.initials: YP
authors.lastname: Lim
authors.forename: Edward
authors.initials: E
authors.lastname: Siryaporn
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: John P
authors.initials: JP
authors.lastname: Pribble
authors.forename: John E
authors.initials: JE
authors.lastname: Palardy
authors.forename: Sonia
authors.initials: S
authors.lastname: Souza
mesh_terms: 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
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; C011877:inter-alpha-inhibitor