Defective pro-IL-1β responses in macrophages from aged mice

Background: Cytokines regulated by the inflammasome pathway have been extensively implicated in various age-related immune pathologies. We set out to elucidate the contribution of the nod-like receptor protein 3 (NLRP3) inflammasome pathway to the previously described deficiencies in IL-1 beta production by macrophages from aged mice. We examined the production of pro-IL-1 beta and its conversion into IL-1 beta as two separate steps and compared these cytokine responses in bone marrow derived macrophages from young (6 8 weeks) and aged (18-24 months) C57BL/6 mice. Findings: Relative to macrophages from young mice, macrophages from aged mice produced less pro-IL-1 beta after TLR4 stimulation with LPS. However upon activation of the NLRP3 inflammasome with ATP, macrophages from young and aged mice were able to efficiently convert and secrete intracellular pro-cytokines as functional cytokines. Conclusions: Lower levels of IL-1 beta production are a result of slower and lower overall production of pro-IL-1 beta in macrophages from aged mice.