The Cytokine Response to Sepsis: IL-6 and LBP

IL-6 and lipopolysaccharide binding protein (LBP) are cytokines (cellular messengers) that are upregulated in the acute phase response to infection and/or inflammation.

Interleukin 6 (IL-6) is a cytokine with both pro- and anti-inflammatory characteristics.

  • Serum levels rise quickly with the onset of SIRS and sepsis1
  • Levels can provide information for risk stratification and prognosis with regard to severity2,3
  • Rising levels correspond with increasing APACHE II scores (an in indicator of illness severity)4
  • Fatal severe sepsis is associated with an early rise in IL-6 to 1000 ng/mL or more4
  • High levels of IL-6 have shown to be predictive of later development of severe sepsis at the onset of hospital-acquired pneumonia and after surgery5,6
  • Rising levels can predict development of kidney injury during severe sepsis7

IL-6 may be of particular value in neonatology and pediatrics:

  • In healthy infants, adult levels are present at birth and remain stable
  • In infants at risk for late-onset neonatal sepsis, IL-6 has been shown to rise up to 48 hours before bacterial sepsis becomes clinically apparent8
  • Increased levels at hospital admission are predictive of septic shock in children9
  • Increased levels at hospital admission are predictive of septic shock and death in pediatric burn patients10

Lipopolysaccharide-binding protein (LBP) recognizes the endotoxin component of the gram-negative bacterial membranes. It also recognizes similar lipid structures found in the membrane of gram-positive bacteria and the walls of pathogenic fungi.11

  • LBP is present constitutively at low levels
  • LBP rises within 24 hours of systemic bacterial or fungal infection11,12
  • LBP can differentiate between bacterial and viral pathogenic sources of sepsis11,12
  • LBP can help differentiate between bacterial pneumonia and nonbacterial acute bronchitis13

LBP is a valuable tool in pediatrics

  • LBP rises in invasive bacterial infection in children14
  • Elevated LBP indicate bacterial infection in neonates ≥ 28 weeks gestation15
  • LBP may be the best differentiator between SIRS and early-onset sepsis in neonates <48 hrs old16

IL-6 and LBP: Infection, inflammation and sepsis

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2. Van Griensven M. Trauma und Infection. II Internationales Symposium: Sepsis, SIRS, Immunantwort. Diagnostik und Therapeutische Ansattze (Abstractband) 2002:24.
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5. Von Dossow V, et al. Crit Care 2005;9(6):R662.
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11. Blairon L, et al. J Infect Dis 2003;187:287-91.
12. Kaden J, et al. Transplantationsmedizin 2001; 13: 52-9.
13. Hopstaken RM, et al. Prim Care Resp J 2009;18:in press.
14. Ubenauf KM, et al. Ped Inf Dis J 2007;26:159-62.
15. Behrendt D, et al. Arch Dis Child Fetal Neonatal Ed 2004;89:F551-4.
16. Pavcnik-Arnol M, et al. Int Care Med 2004;30:1454-60.