title: Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock.
abstract: OBJECTIVE
  Resistin induces insulin resistance in mice. In humans, recent data suggest that resistin functions as a proinflammatory cytokine. Here, we studied resistin up to 2 wks after admission in patients with septic shock and/or severe sepsis.
  
  
  METHODS
  Two prospective studies of patients with sepsis and in vitro studies of resistin interaction with monocytes.
  
  
  METHODS
  Intensive care unit at Karolinska University Hospital and Center for Infectious Medicine, Karolinska Institute, Huddinge, Sweden.
  
  
  METHODS
  Twenty-nine patients with severe sepsis and 66 with septic shock.
  
  
  METHODS
  None.
  
  
  RESULTS
  Ninety-five patients were studied, 25 of whom died within 28 days. Resistin and cytokine levels and routine biochemistry were measured at three to six defined time points during the first 2 wks after admission and were correlated to other cytokines, glucose levels, body mass index, Acute Physiology and Chronic Health Evaluation II, and Sepsis-related Organ Failure Assessment scores. Serum resistin was significantly elevated compared with healthy controls (p < .000001) and correlated with severity of disease as measured by Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores, with an increasingly strong degree of correlation over time. Median levels were four- to eight-fold higher than controls and remained high up to 2 wks after admission to the intensive care unit. Levels correlated with interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, creatinine, D-dimer, and lactate, but not with p-glucose or body mass index. In vitro, resistin was released from monocytes after stimulation with either lipopolysaccharide or high mobility group box 1 protein. Recombinant resistin itself up-regulated intercellular adhesion molecule-1 on monocytes.
  
  
  CONCLUSIONS
  This is the first study assessing systemic levels of resistin in patients with septic shock/severe sepsis. We show that resistin is a marker of severity of disease and possibly a mediator of the prolonged inflammatory state seen in infected critically ill patients. Further exploration of resistin as a therapeutic target and marker of disease is merited.
authors: Department of Medicine, Division of Infectious Diseases, Center for Infectious Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Sweden. jonas.sunden-cullberg@ki.se
authors: Jonas
authors: J
authors: Sundén-Cullberg
authors: Thomas
authors: T
authors: Nyström
authors: Martin L
authors: ML
authors: Lee
authors: Gail E
authors: GE
authors: Mullins
authors: Leif
authors: L
authors: Tokics
authors: Jan
authors: J
authors: Andersson
authors: Anna
authors: A
authors: Norrby-Teglund
authors: Carl Johan
authors: CJ
authors: Treutiger
mesh_terms: D018806:APACHE; D016470:Bacteremia / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose; D015992:Body Mass Index; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011446:Prospective Studies; D052243:Resistin / Q000096:biosynthesis*; D018805:Sepsis / Q000097:blood / Q000378:metabolism*; D012772:Shock, Septic / Q000097:blood / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D052243:Resistin