Immunologic Changes in Frail Older Adults

Several studies have shown a heightened inflammatory state in frail older adults, marked by high serum levels of interleukin-6 and C-reactive protein and an increased number of circulating leukocytes. Activation of monocytes and macrophages, marked by increased levels of neopterin, may contribute to chronic inflammation in the frail older adult. However, the reduced mononuclear cell response to lipopolysaccharide in vitro suggests the existence of defective activation pathways within the innate immune system possibly due to desensitization. Conversely, the expansion of CD8(+) T cells, and specifically those expressing the CCR5 chemokine receptor, above and beyond the levels observed in senescence, points to the involvement of adaptive immune pathways. In line with these observations, frail older adults exhibit a reduced antibody response to pneumococcal and influenza vaccines. Collectively, these observations support the existence of a dysregulated immune system in frail older adults and highlight the need for strategies to improve its function. ABBREVIATIONS: AIDS, acquired immunodeficiency syndrome; CCL, CC-chemokine receptor ligand; CCR, CC-chemokine receptor; CHS, Cardiovascular Health Study; CMV, cytomegalovirus; GTP, guanosine trisphosphate; HAART, highly active anti-retroviral therapy; HIV, human immunodeficiency virus; IDO, indoleamine-pyrrole 2,3-dioxygenase; IL, interleukin; IFN, interferon; MACS, Multicenter AIDS Cohort Study; NH2PPP, dihydro-neopterin trisphosphate; Tc, T cytotoxic; TCR, T-cell receptor; TEMRA, T effector memory cells re-expressing CD45RA; Th, T helper; TNF, tumor necrosis factor; WHAS, Women’s Health and Aging Study