Intensive Care Medicine

, Volume 37, Issue 3, pp 525–532 | Cite as

Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome

  • Mark W. Hall
  • Nina L. Knatz
  • Carol Vetterly
  • Steven Tomarello
  • Mark D. Wewers
  • Hans Dieter Volk
  • Joseph A. CarcilloEmail author
Pediatric Original



Immunoparalysis defined by prolonged monocyte human leukocyte antigen DR depression is associated with adverse outcomes in adult severe sepsis and can be reversed with granulocyte macrophage colony-stimulating factor (GM-CSF). We hypothesized that immunoparalysis defined by whole-blood ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha (TNFα) response <200 pg/mL beyond day 3 of multiple organ dysfunction syndrome (MODS) is similarly associated with nosocomial infection in children and can be reversed with GM-CSF.


In study period 1, we performed a multicenter cohort trial of transplant and nontransplant multiple organ dysfunction syndrome (MODS) patients (≥2 organ failure). In study period 2, we performed an open-label randomized trial of GM-CSF therapy for nonneutropenic, nontransplant, severe MODS patients (≥3 organ failure) with TNFα response <160 pg/mL.


Immunoparalysis was observed in 34% of MODS patients (n = 70) and was associated with increased nosocomial infection (relative risk [RR] 3.3, 95% confidence interval [1.8–6.0] p < 0.05) and mortality (RR 5.8 [2.1–16] p < 0.05). TNFα response <200 pg/mL throughout 7 days after positive culture was associated with persistent nosocomial infection, whereas recovery above 200 pg/mL was associated with resolution of infection (p < 0.05). In study period 2, GM-CSF therapy facilitated rapid recovery of TNFα response to >200 pg/mL by 7 days (p < 0.05) and prevented nosocomial infection (no infections in seven patients versus eight infections in seven patients) (p < 0.05).


Similar to in adults, immunoparalysis is a potentially reversible risk factor for development of nosocomial infection in pediatric MODS. Whole-blood ex vivo TNFα response is a promising biomarker for monitoring this condition.


Immunoparalysis Immune suppression withdrawal GM-CSF TNFα IL-6 



The authors would like to acknowledge Patricia Guittar, RN for her assistance with subject identification and enrollment. This study was funded in part by NCRR 3M01RR0056GCRC (J.A.C.), NICHD K12 HD43372 (M.W.H.), NHLBI K08 HL085525 (M.W.H.), Deutsche Froschungsgemeinschaft SFB 421 (H.D.V.), and The Research Institute at Nationwide Children’s Hospital (M.W.H.).

Supplementary material

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Supplementary material 1 (DOC 1944 kb)


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Copyright information

© Copyright jointly held by Springer and ESICM 2010

Authors and Affiliations

  • Mark W. Hall
    • 1
    • 2
  • Nina L. Knatz
    • 2
  • Carol Vetterly
    • 3
  • Steven Tomarello
    • 3
  • Mark D. Wewers
    • 4
  • Hans Dieter Volk
    • 5
  • Joseph A. Carcillo
    • 3
    • 6
    Email author
  1. 1.Department of Pediatrics, Section of Critical Care MedicineThe Ohio State University College of MedicineColumbusUSA
  2. 2.The Research Institute at Nationwide Children’s HospitalColumbusUSA
  3. 3.Children’s Hospital of PittsburghPittsburghUSA
  4. 4.Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal MedicineThe Ohio State University College of MedicineColumbusUSA
  5. 5.Department of Medical Immunology and Berlin-Brandenburg Center for Regenerative TherapiesCharité University Medicine BerlinBerlinGermany
  6. 6.Departments of Critical Care Medicine and PediatricsUniversity of Pittsburgh School of MedicinePittsburghUSA

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