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
1. Woiciechowsky C, et al. J Trauma 2002; 52: 339-45.
2. Van Griensven M. Trauma und Infection. II Internationales Symposium: Sepsis, SIRS, Immunantwort. Diagnostik und Therapeutische Ansattze (Abstractband) 2002:24.
3. Wakefield CH, et al. Brit J Surg 1998; 85: 818-825.
4. Kinasewitz GT, et al. Crit Care 2004;8(2):R82.
5. Von Dossow V, et al. Crit Care 2005;9(6):R662.
6. Mokart D, et al. Brit J Anaes 2005;94:767-73.
7. Chawla LS, et al. Clin J Am Soc Nephrol 2007;2:22.
8. Küster H, et al. Lancet 1998;352:1271-77.
9. Fioretto JR, et al. Cytokine 2008; 43:160-164.
10. Finnerty CC, et al. Shock 2007; 27:4-9.
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.