Abstract
Separate bodies of literature report that elevated pro-inflammatory cytokines and cortisol negatively affect hippocampal structure and cognitive functioning, particularly in older adults. Although interactions between cytokines and cortisol occur through a variety of known mechanisms, few studies consider how their interactions affect brain structure. In this preliminary study, we assess the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight community-dwelling older adults underwent blood draws for quantification of circulating cytokines and saliva collections to quantify the cortisol awakening response. Hippocampal volume measurements were made using structural magnetic resonance imaging. Elevated levels of waking cortisol in conjunction with higher concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF-alpha were also associated with smaller hippocampal volumes. These data provide preliminary evidence that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, are associated with smaller hippocampal volume in older adults. We suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis and inflammation processes may explain hippocampal volume reductions in older adults better than either set of measures do in isolation.
Highlights
Cytokines are small proteins, which are produced by a variety of immune cells and are critically important for cell signaling during when the immune system is mounting inflammatory responses to infection and cell damage
Significant interactions between cortisol and cytokine measures were observed. These interactions were between cortisol and both IL-6 (β = −0.42, p = 0.037; See Figures 1, 2) and TNFalpha (β = −0.43, p = 0.047; See Figures 1, 3)
Having concurrently high cytokine levels and high waking cortisol levels was associated with smaller hippocampal volumes
Summary
Cytokines are small proteins, which are produced by a variety of immune cells (lymphocytes, macrophages, natural killer cells etc.) and are critically important for cell signaling during when the immune system is mounting inflammatory responses to infection and cell damage. Specific cytokines e.g., IL-6, have been found to be inversely correlated with hippocampal gray matter volumes (Tanabe et al, 1997; Marsland et al, 2008) and can adversely affect hippocampal morphology during development in animal models (Kraemer and Blasey, 2004; Samuelsson et al, 2006). Both IL-1Beta and TNFAlpha have been shown to inhibit long-term potentiation and synaptic plasticity in the hippocampus and potentially contribute to excitotoxicity (Marques-Deak et al, 2005; Hermann et al, 2006; Pickering and O’Connor, 2007). In humans TNF-alpha single nucleotide polymorphisms predict smaller hippocampal volumes (Chapman et al, 1987; Spath-Schwalbe et al, 1998; Baune et al, 2012)
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