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

• Normal aging alters the time-dependent response to a pro-inflammatory challenge.
• Age and young rats differ in how their brains translate cytokine mRNA into proteins.
• Age rats demonstrate an exaggerated response to a pro-inflammatory challenge.

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.