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 severity^2,3
• 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 surgery^5,6
• 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 infection^11,12
• LBP can differentiate between bacterial and viral pathogenic sources of sepsis^11,12
• 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