Inflammatory status in sepsis alters efficacy of interleukin-18 binding protein therapy.

Abstract

OBJECTIVE:

Sepsis remains a serious clinical problem, and multiple attempts at blocking inflammation have failed to decrease mortality rate. Interleukin-18 has been demonstrated to be an important component of the innate immune response to bacterial infections.

DESIGN:

Previous work demonstrated that elevated plasma concentrations of interleukin-6 obtained in the first 6 hrs of sepsis predict a worse outcome. Mice were subjected to cecal ligation and puncture and, on the basis of the plasma concentration of interleukin-6, were randomized to receive either interleukin-18 binding protein or vehicle approximately 8 hrs after the onset of sepsis.

SETTING:

University research laboratory.

SUBJECTS:

Adult, female BALB/c mice.

INTERVENTIONS:

We sought to determine the role of interleukin-18 in sepsis by blocking its biological activity with the interleukin-18 binding protein in the murine model of sepsis induced by cecal ligation and puncture.

MEASUREMENTS AND MAIN RESULTS:

In this study, elevated plasma concentrations of interleukin-6 were associated with a worse outcome. Treatment with interleukin-18 binding protein decreased inflammation as determined by lower concentrations of plasma interleukin-6 obtained 48 hrs after the onset of sepsis. In mice with increased risk of dying, interleukin-18 binding protein slightly decreased mortality rate. However, in those mice with a predicted low mortality rate, interleukin-18 binding protein significantly increased mortality rate.

CONCLUSIONS:

In this study, mice at low risk of death due to sepsis had decreased survival when treated with interleukin-18 binding protein. These results have potential implications for the use of interleukin-18 binding protein for treatment of chronic inflammatory conditions since it may place the host at increased risk of infectious complications.

• Authors: Daniel G Remick, Gerald E Bolgos, Javed Siddiqui
• Journal: Critical care medicine (Crit Care Med) Vol. 31 Issue 8 Pg. 2096-101 (Aug 2003) ISSN: 0090-3493 [Print] United States
• PMID: 12973165 (Publication Type: Journal Article)

Chemical References

• Glycoproteins
• Intercellular Signaling Peptides and Proteins
• Interleukin-6
• interleukin-18 binding protein

Topics

• Animals
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Female
• Glycoproteins (administration & dosage, pharmacology, therapeutic use)
• Inflammation (blood)
• Injections, Intraperitoneal
• Intercellular Signaling Peptides and Proteins
• Interleukin-6 (blood)
• Mice
• Mice, Inbred BALB C
• Sepsis (blood, drug therapy)
• Survival Analysis