Age-associated alterations in the time-dependent profile of pro- and anti-inflammatory proteins within the hippocampus in response to acute exposure to interleukin-1β

J Neuroimmunol. 2014 Feb 15;267(1-2):86-91. doi: 10.1016/j.jneuroim.2013.12.010. Epub 2013 Dec 22.

Abstract

The pro-inflammatory cytokine IL-1β is known to play a role in several models of aging, neuroinflammation, and neurodegenerative diseases. Here, we document a detailed time- and age-dependent pattern of pro- and anti-inflammatory biomarkers following bilateral intrahippocampal injection of interleukin-1β. During the first 12h several pro- and anti-inflammatory cytokines increased in the aged (24 mo old) rats, some of which returned to baseline levels by 24h post-injection while others remained elevated for 72 h post-injection. In contrast, no such increases were observed in the young (3 mo old) rats. Interestingly, young rats up-regulated mRNA of two pro-inflammatory cytokines, interleukin-1β and tumor necrosis factor-α, but did not translate these transcripts into functional proteins, which may be related to expression of suppressor of cytokine signaling type-2. These results contribute to our understanding of how neuroinflammation may contribute to the pathogenesis of age-related neurodegenerative disorders due to an age-related bias towards a hyper-reactive immune response that is not selective for a pro- or anti-inflammatory phenotype following an inflammatory stimulus.

Keywords: Aging; Cytokines; Hippocampus; Microglia; Neuroinflammation; Rat.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Analysis of Variance
  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression Regulation / drug effects
  • Hippocampus / drug effects*
  • Interleukin-1beta / pharmacology*
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism
  • Signal Transduction / drug effects*
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Cxcr3 protein, rat
  • Cytokines
  • Interleukin-1beta
  • RNA, Messenger
  • Receptors, CXCR3
  • Socs2 protein, rat
  • Suppressor of Cytokine Signaling Proteins
  • p38 Mitogen-Activated Protein Kinases