Lipopolysaccharide-stimulated intracellular cytokines and depressive symptoms in community-dwelling older adults

Background: Inflammation is involved in the pathophysiology of depression, and circulating inflammatory cytokines have been associated with depressive symptoms. However, measuring circulating cytokines have inherent methodological limitations. In vitro lipopolysaccharide (LPS)-stimulated intracellular cytokines (ICCs) overcome these limitations. Furthermore, because psychosocial and physiological stressors activate inflammatory responses and LPS-stimulated ICCs reflect the inflammatory responsivity of monocytes to such stressors, ICCs may reflect individual stress responsivity. Methods: This cross-sectional study examined whether LPS-stimulated expression of ICCs in peripheral blood mononuclear cells (PBMCs) is a sensitive inflammation measure correlated with depressive symptoms in 180 community-dwelling older adults. We tested correlations of not only intracellular but also circulating inflammatory markers with depressive symptoms assessed using the 10-item Center for Epidemiological Studies Depression Scale (CES-D). Intracellular markers included expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and both in PBMCs. Circulating markers included IL-6, TNF-alpha, and C-reactive protein (CRP) in plasma. Results: None of the correlations were statistically significant. However, in contrast to circulating markers, the correlations of ICCs were consistently in the expected direction, i.e., higher ICC expression correlating with higher depression severity. Discussion: Despite the non-significant findings, further research is required for the evaluation of LPS-stimulated ICC expression as biomarkers of depressive symptoms.