IMMUNE DYSREGULATION IN THE AGING HUMAN LUNG

Aging has been associated with diminished lung function and increased susceptibility to lung infection. To determine whether changes suggest ive of immune dysregulation and inflammation appear in the lungs of cl inically normal individuals as a function of advancing age, we perform ed bronchoalveolar lavage (BAL) on discontinuous age groups (20-36, 45 -55, and 65-78 yr old) of clinically normal volunteer subjects. We mea sured immunoglobulin (IgG IgA, IgM), albumin, interleukin-6 (IL-6), an d interleukin-10 concentrations in BAL fluid. Bronchoalveolar cell pro files, cell surface antigen expression, and superoxide anion productio n were also measured. A significant increase in total cell concentrati on, neutrophils, and BAL immunoglobulin content was observed in the ol dest age group compared with the youngest age group. Mean lymphocyte s ubset (CD4(+)/CD8(+)) ratios were significantly increased in blood (2. 6 +/- 0.4 versus 1.6 +/- 0.1; p < 0.03) and to a greater degree in BAL (4.8 +/- 1.0 versus 1.9 +/- 0.2; p < 0.01) for the oldest versus youn gest age groups. Similarly, BAL-derived cells displayed significantly increased phorbol myristate acetate-stimulated release of superoxide a nion (8.8 +/- 1.3 versus 4.5 +/- 0.7 nmol/5 x 10(5) cells/h; p < 0.01) for the oldest versus youngest subject group, and mean BAL IL-6 conce ntrations were significantly elevated in the oldest age group (0.86 +/ - 0.13 ng/ml) compared with the youngest age group (0.53 +/- 0.03 ng/m l; p < 0.01). Our observations suggest that altered inflammatory cell profiles and low-grade inflammation exist in the lower respiratory tra cts of many asymptomatic, clinically normal volunteers of advanced age .