Socioeconomic disadvantage, chronic stress, and proinflammatory phenotype: an integrative data analysis across the lifecourse

Abstract

Socioeconomic disadvantage confers risk for many chronic illnesses, and theories have highlighted chronic psychological stress and alterations to inflammatory processes as key pathways. Specifically, disadvantage can heighten chronic stress, which may promote a pro-inflammatory phenotype characterized by immune cells mounting exaggerated cytokine responses to challenge and being less sensitive to inhibitory signals. Importantly, lifecourse perspectives emphasize that such immune alterations should be more potent earlier in life during a sensitive period when bodily tissues are highly plastic to environmental inputs. However, examining these propositions is resource intensive, as they require cell-culturing approaches to model functional inflammatory activities, a wide age range, and longitudinal data. Here, we integrated data from five independent studies to create a diverse sample of 1,607 individuals (960 with longitudinal data; 8–64 years old; 359 Asian, 205 Black, 151 Latino/a). Leveraging the resulting lifecourse data, rich interview assessments of disadvantage and stress, and ex-vivo assessments of inflammation, we examined two questions: (1) Does chronic stress account for the link between disadvantage and pro-inflammatory phenotype? (2) Is there a developmental period during which inflammatory responses are more sensitive to disadvantage and chronic stress? Disadvantage was associated with higher chronic stress, which was linked with a pro-inflammatory phenotype cross-sectionally, longitudinally, and in terms of prospective change across 1.5 to 2 years. Consistent with the sensitive period hypothesis, the magnitude of these indirect associations was strongest in earlier decades and declined across the lifecourse. These findings highlight the importance of taking a lifecourse perspective in examining health disparities.

Impact of Preoperative Quality of Life and Related Factors on the Development of Surgical Site Infections Following Primary Total Joint Arthroplasty: A Prospective Case-Control Study with a Five-Year Follow-Up

“…Symptomatic osteoarthritis is a cause of chronic stress because patients have difficulty in performing daily activities and may be socially isolated because of their disability to move, resulting in a low score in the QoL questionnaire. Indeed, increased chronic stress promotes a proinflammatory phenotype characterised by the ascendance of immune cells and elevated production of cytokines, accompanied by a reduction of inhibitory signals [ 20 ]. Additionally, recent experimental data in humans and animal models has shown that stress induces a hyperinflammatory state in myeloid cells that is accompanied by alterations in chromatin structure at inflammatory and metabolic gene loci, elevated expression of inflammatory genes, and increased cytokine secretion [ 21 ].…”

Annual Research Review: Neuroimmune network model of depression: a developmental perspective

“…The monocytes of children living in adversity also become less sensitive to inhibitory signals, such as glucocorticoids and primarily anti‐inflammatory cytokines (e.g. IL‐10), which further dysregulates the inflammatory response (Lam, Chen, Chiang, & Miller, 2022; Schreier, Roy, Frimer, & Chen, 2014). This insensitivity may be adaptive during acute threats but under conditions of chronic stress could facilitate low‐grade and nonresolving chronic inflammation (Miller et al., 2011).…”

Family Disadvantage, Education, and Health Outcomes Among Black Youths Over a 20-Year Period

“…Mechanistically, experiences of stress earlier in life are known to calibrate the response tendencies of innate immune cells so they mount excessive inflammatory responses to microbial challenges and become insensitive to glucocorticoid hormones that regulate these responses. 13,19 This response tendency has been termed a proinflammatory phenotype. 13 To assess proinflammatory phenotypes, we used a portable cell culture protocol developed for field settings, 33 where immune cells are incubated ex vivo with a bacterial product (lipopolysaccharide [LPS]), and production of the proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α were measured.…”