The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function

• DOI: 10.1189/jlb.0804449
• Publication Date: 2005-01-04T01:12:45Z
• Authors: R Lakshman Chelva...; Sarah M Collins; Juliana M Van Wil...; Subbarao Bondada
• Keywords: Inflammation; Lipopolysaccharides; 0301 basic medicine; Aging; B-Lymphocytes; Mice, Inbred BALB C; Interleukin-6; Macrophages; Interleukin-10; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Picrates; Animals; Ficoll; Lymphocytes; Spleen

Abstract A reduction in macrophage (MΦ) function with aging makes mice less responsive to bacterial capsular polysaccharides, such as those present the pneumococcal polysaccharide vaccine, a model of thymus independent (TI) antigen (Ag). Using trinitrophenol (TNP)-lipopolysaccharide (LPS) and TNP-Ficoll, two other well-studied TI Ag, we studied mechanistic basis reduced MΦ aged. We show that aged are profoundly hyporesponsive these Ag. As result requirement for MΦ, highly purified B cells from young-adult do not respond When purified, young were immunized antibody production cultures reconstituted was significantly lower than seen MΦ. Consequently, this unresponsiveness can be overcome by mixture interleukin (IL)-1β IL-6. Upon stimulation LPS, comparison secreted amounts IL-6, tumor necrosis factor α, IL-1β, IL-12, cytokines necessary LPS also induced produce an excess IL-10. Neutralization IL-10 enhanced proinflamatory upon Ab splenocytes. Thus, inability help cell response appears caused have number expressing Toll-like receptor 4 CD14, imbalance cytokine might partly fewer key components complex.