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.
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
Maribel G
MG
Vallespi
M
M
Colas
H
H
Garay
O
O
Reyes
M J
MJ
Araña
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)