Recovery from an acute systemic and central LPS-inflammation challenge is affected by mouse sex and genetic background

PLoS One. 2018 Aug 22;13(8):e0201375. doi: 10.1371/journal.pone.0201375. eCollection 2018.

Abstract

Genetic and sexual factors influence the prevalence and the pathogenesis of many inflammatory disorders. In this study their relevance on the peripheral and central inflammatory status induced by a peripheral injection of lipopolysaccharide (LPS) was evaluated. BALB/c and CD-1 male and female mice were intraperitoneally injected with LPS. Spleens and brains were collected 2 and 72 hours later to study the levels of IL-6, TNF-α and IL-1β. Percentage of microglia and astrocytes was determined in the cortex and hippocampus. Locomotor activity was registered before and during the 72 hours after LPS-treatment. Two hours after LPS-injection, a peripheral increase of the three cytokines was found. In brains, LPS increased TNF-α only in males with higher levels in CD-1 than BALB/c. IL-1β increased only in CD-1 males. IL-6 increased in both strains with lower levels in BALB/c females. Peripheral and central levels of cytokines decline 72 hrs after LPS-treatment whilst a significantly increase of Iba-1 expression was detected. A dramatic drop of the locomotor activity was observed immediately after LPS injection. Our results show that acute systemic administration of LPS leads to peripheral and central increase of pro-inflammatory cytokines and microglia activation, in a strain and sex dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain* / immunology
  • Brain* / physiology
  • Female
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microglia* / immunology
  • Microglia* / pathology
  • Monokines* / genetics
  • Monokines* / immunology
  • Organ Specificity / genetics
  • Organ Specificity / immunology
  • Sex Characteristics
  • Species Specificity
  • Spleen* / immunology
  • Spleen* / pathology
  • Systemic Inflammatory Response Syndrome* / chemically induced
  • Systemic Inflammatory Response Syndrome* / genetics
  • Systemic Inflammatory Response Syndrome* / immunology
  • Systemic Inflammatory Response Syndrome* / pathology

Substances

  • Lipopolysaccharides
  • Monokines

Grants and funding

This work was supported by Dirección General de Personal Académico, UNAM (DGAPA-UNAM, grant IN211917 to E.S.), México. This study was also supported by the Institutional program "Programa de Investigación para el Desarrollo y la Optimización de Vacunas, Inmunomoduladores y Métodos Diagnósticos del Instituto de Investigaciones Biomédicas" U.N.A.M., and by CONACYT-SALUD-2015-C01-261455 to L.A-P. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.