Differential regulation of Th1/Th2 in relevant tissues for sepsis pathogenesis with a Limulus anti-LPS factor-derived peptide increases survival in Gram-positive sepsis.

Abstract

Severe sepsis and septic shock are important causes of death in intensive care units. Although Gram-negative infections were predominant in the 1960s, Gram-positive infections have increased in the past two decades and now account for about half of the cases of severe sepsis. In this study, we examined the effect of a Limulus anti-LPS factor (LALF)-derived peptide on lung and liver Th1/Th2 cytokine mRNA levels during a Gram-positive sepsis. We also examined the morphopathological changes observed in these organs during the disease. Mice challenged with a high dose of Staphylococcus haemolyticus showed severe damage in lung. In contrast, the liver of challenged mice showed an accumulation of bacterial particles in the sinusoids, associated with a severe inflammatory response due to high levels of tissue mRNA proinflammatory cytokines. Treatment with the peptide LALF(32-51) ameliorated the sepsis-induced effects in the lung and liver and increased the survival of mice in a dose- and time-dependent manner. Pretreatment with the peptide LALF(32-51) differentially regulates TNF-alpha, IFN-gamma, IL-12p40, IL-2 and IL-10 mRNA levels in lung and liver of peptide-treated mice, and limits the systemic inflammatory response. These findings support for the first time the effectiveness of an LALF-derived peptide in the treatment of a Gram-positive sepsis. Modulation of the Th1/Th2 pattern in tissues relevant for sepsis correlates with an improved outcome of the disease as denoted by increased survival.

• Authors: Maribel G Vallespi, M Colas, H Garay, O Reyes, M J Araña
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 4 Issue 10-11 Pg. 1343-51 (Oct 2004) ISSN: 1567-5769 [Print] Netherlands
• PMID: 15313432 (Publication Type: Journal Article)

Chemical References

• Anti-Infective Agents
• Antimicrobial Cationic Peptides
• Arthropod Proteins
• Cytokines
• Invertebrate Hormones
• Peptide Fragments
• RNA, Messenger
• antilipopolysaccharide factor (Limulus)

Topics

• Animals
• Anti-Infective Agents (pharmacology, therapeutic use)
• Antimicrobial Cationic Peptides
• Arthropod Proteins
• Cytokines (blood, genetics)
• Gene Expression Regulation
• Invertebrate Hormones (chemistry)
• Liver (pathology)
• Lung (pathology)
• Mice
• Mice, Inbred BALB C
• Peptide Fragments (chemistry, pharmacology, therapeutic use)
• RNA, Messenger (blood)
• Sepsis (immunology, mortality, prevention & control)
• Staphylococcal Infections (immunology, mortality, prevention & control)
• Staphylococcus haemolyticus
• Survival Rate
• Th1 Cells (immunology)
• Th2 Cells (immunology)
• Time Factors