Understanding the impact of age-related immunosenescence on immune tolerance of primary human monocytes

Abstract

Immunosenescence, the age-related decline in immune function, significantly impacts sepsis prognosis, a syndrome marked by dysregulated host responses to infection and multi-organ dysfunction. The elderly are disproportionately affected, showing increased pro-inflammatory responses and sustained immune suppression, often exacerbated by chronic conditions. In this study, primary human monocytes from healthy younger (18-30 years; n=7) and older donors (>65 years; n=8) were purified and exposed to lipopolysaccharide (LPS; endotoxin) in a re-stimulation protocol to establish endotoxin tolerance. Flow cytometry confirmed preserved monocyte immunocompetence in both groups, with high CD14 and HLA-DR expression. TNF-α production was measured as inflammatory marker. Elderly donors trended higher TNF-α levels after initial exposure to LPS for four hours, but differences between age groups were not statistically significant. After re- stimulating monocytes, no differences were determined in establishing endotoxin tolerance between groups, suggesting that ageing does not alter the capacity of monocytes to become tolerant.