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

• Published in: Journal of neuroimmunology 2014-02, Vol.267 (1), p.86-91
• Main Authors: Hopp, Sarah C, Royer, Sarah, Brothers, Holly M, Kaercher, Roxanne M, D'Angelo, Heather, Bardou, Isabelle, Wenk, Gary L
• Format: Article
• Language: English
• Subjects: Aging; Allergy and Immunology; Analysis of Variance; Animals; Cytokines; Cytokines - genetics; Cytokines - metabolism; Gene Expression Regulation - drug effects; Hippocampus; Hippocampus - drug effects; Interleukin-1beta - pharmacology; Male; Microglia; Neuroinflammation; Neurology; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Rat; Rats; Rats, Inbred F344; Receptors, CXCR3 - genetics; Receptors, CXCR3 - metabolism; RNA, Messenger - metabolism; Signal Transduction - drug effects; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - metabolism; Time Factors
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2013.12.010

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 12 h several pro- and anti-inflammatory cytokines increased in the aged (24 mo old) rats, some of which returned to baseline levels by 24 h 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.