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

Abstract

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-α (TNF-α), and both in PBMCs. Circulating markers included IL-6, TNF-α, 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.

Alcohol use disorder (AUD) is associated with enhanced sensitivity to cellular lipopolysaccharide challenge

“…IL‐6 is well‐studied as an inflammatory marker in psychiatric disorders. Previous studies, especially in the depression literature, have demonstrated effects of LPS stimulation on IL‐6 (Cho et al, 2019; Irwin et al, 2006). In the alcohol field, IL‐6 has been emphasized as an important marker associated with chronic alcohol exposure (Moura et al, 2022) and withdrawal (Gruol et al, 2018; Roberts et al, 2019).…”

“…A novel method to characterize mechanisms of AUD‐related immune signaling is to probe monocyte production of intracellular cytokines at rest and following in vitro TLR4 stimulation with LPS. This method provides insight into the source of systemic inflammation, independent of extracellular levels (Cho et al, 2019). Monocytes comprise approximately 5% of circulating leukocytes and are a major contributor to proinflammatory cytokine production in peripheral blood (O'Connor et al, 2007).…”