title: Dendritic cells from the elderly display an intrinsic defect in the production of IL-10 in response to lithium chloride.
abstract: Chronic, low grade inflammation is a characteristic of old age. Innate immune system cells such as dendritic cells (DCs) from the elderly display a pro-inflammatory phenotype associated with increased reactivity to self. Lithium is a well-established anti-inflammatory agent used in the treatment of bipolar disorders. It has also been reported to reduce inflammation in DCs. Here, we investigated whether Lithium is effective in reducing the inflammatory responses in DCs from the elderly. The effect of Lithium Chloride (LiCl) was compared on the response of TLR4 agonist, LPS and TLR2 agonist, PAM3CSK4 stimulated aged and young DCs. LiCl enhanced the production of IL-10 in LPS stimulated young DCs. However, it did not affect TNF-α and IL-6 production. In contrast, in aged DCs, LiCl reduced the secretion of TNF-α and IL-6 in LPS stimulated DCs but did not increase IL-10. LiCl had no significant effect on PAM3CSK4 responses in aged and young DCs. LiCl treated DCs also displayed differences at the level of CD4 T cell priming and polarization. LPS-stimulated young DCs reduced IFN-γ secretion and biased the Th cell response towards Th2/Treg while LiCl treated aged DCs only reduced IFN-γ secretion but did not bias the response towards Th2/Treg. In summary, our data suggests that LiCl reduces inflammation in aged and young DCs via different mechanisms. Furthermore, the effect of LiCl is different on LPS and PAM3CSK4 responses.
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Agrawal
authors.forename: Sastry
authors.initials: S
authors.lastname: Gollapudi
authors.forename: Sudhir
authors.initials: S
authors.lastname: Gupta
authors.forename: Anshu
authors.initials: A
authors.lastname: Agrawal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000819:agonists; D051197:Toll-Like Receptor 4 / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D018122:B7-1 Antigen; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008074:Lipoproteins; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; D016753:Interleukin-10; D018021:Lithium Chloride
keywords: Aging; Dendritic cells; Human; Lithium Chloride; TLR2; TLR4