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.
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.
Vallespi
Maribel G
MG
Division of Physics and Chemistry, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Avenue 31 e/158 y 190, Cubanacan, Playa, La Havana, CP 10600, Cuba. maribel.guerra@cigb.edu.cu
Colas
M
M
Garay
H
H
Reyes
O
O
Araña
M J
MJ
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D016207:Cytokines / Q000097:blood / Q000235:genetics; D005786:Gene Expression Regulation; D007447:Invertebrate Hormones / Q000737:chemistry*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000097:blood; D018805:Sepsis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D041162:Staphylococcus haemolyticus; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D016207:Cytokines; D007447:Invertebrate Hormones; D010446:Peptide Fragments; D012333:RNA, Messenger; C034705:antilipopolysaccharide factor (Limulus)