Inflammatory biomarkers in older adults with frailty: a systematic review and meta-analysis of cross-sectional studies

Systemic chronic inflammation has been proposed as an essential mediating factor in frailty, and several studies tested its relationship with frailty. However, the issue is still controversial.We identified observational studies and pooled their results to assess whether abnormal expression of inflammatory biomarkers is present in the blood of older adults with frailty.We conducted a systematic search on the Medline, Embase, and Web of Science database from inception to 1st September 2021. The quality of included studies was assessed using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies (JBI-MAStARI). Study heterogeneity was assessed with the Cochran Q test and I2 statistic. Pooled estimates were obtained through random-effect models. Sensitivity analyses were conducted by excluding one of the studies. Egger's regression test and observation of funnel plots were used to detect small-study effects and publication bias. PROSPERO registration: CRD42020172853.A total of 53 cross-sectional studies corresponding to 56 independent study populations were included in this analysis. There were 31 study populations with three frailty categories (3144 frailty, 14,023 pre-frailty, 10,989 robust) and 25 study populations with two frailty categories (2576 frailty, 8368 non-frailty). This meta-analysis performed pooled analyses for the inflammatory biomarker leukocyte, lymphocytes, CRP, IL-6, IL-10, and TNF-α. Older adults with frailty had lower lymphocytes and higher interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels compared with the control group. However, there was no significant difference in leukocyte and IL-10 levels in the two groups.These findings suggest that peripheral inflammatory biomarkers lymphocytes, IL-6, CRP, and TNF-α are related to frailty status. Our findings are not conclusive regarding the causal relationship between chronic inflammation and frailty, so the development of further longitudinal and well-designed studies focused on this is necessary.