Infectious Arthritis in the Elderly

  • Nicole Melendez
  • Luis R. EspinozaEmail author


Infections have long been known to be leading causes of morbidity and mortality in the elderly population. Immunosenescence of both the innate and adaptive immune systems contributes largely to this and we have examined the studies which show changes in toll-like receptors (TLRs), cytokines, dendritic cells, antibody response, and T-cells. Theses changes, in addition to functional changes, lead to increased infections in the elderly population.


Infection T-cells Immunosenescence 


  1. 1.
    Leading Causes of Death, 1900–1998, Center for Disease Control. At: Accessed Oct 12, 2008.
  2. 2.
    Solana R, Pawelec G, Tarazona R. Aging and innate immunity. Immunity. 2006;24:491–4.PubMedCrossRefGoogle Scholar
  3. 3.
    Gavazzi G, Krause KH. Ageing and infection. Lancet Infect Dis. 2002;2:659–66.PubMedCrossRefGoogle Scholar
  4. 4.
    Small L, Ross J. Suppurative tenosynovitis and septic bursitis. Infect Dis Clin N Am. 2005;19:991–1005.CrossRefGoogle Scholar
  5. 5.
    Gavet F, Tournadre A, Soubrier M, Ristori JM, Dubost JJ. Septic arthritis in patients aged 80 and older: a comparison with younger adults. J Am Geriatr Soc. 2005;7:1210–3.CrossRefGoogle Scholar
  6. 6.
    Geiger H, Van Zant G. The aging of lympho-hematopoietic stem cells. Nat Immunol. 2002;3:329–33.PubMedCrossRefGoogle Scholar
  7. 7.
    Henckaerts E, Geiger H, Langer JC, Rebollo P, Van Zant G, Snoeck HW. Genetically determined variation in the number of phenotypically defined hematopoietic progenitor and stem cells and in their response to early-acting cytokines. Blood. 2002;11:3947–54.CrossRefGoogle Scholar
  8. 8.
    De Haan G et al. A genetic and genomic analysis identifies a cluster of genes associated with hematopoietic cell turnover. Blood. 2002;6:2056–62.CrossRefGoogle Scholar
  9. 9.
    Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL. The aging of hematopoietic stem cells. Nat Med. 1996;9:1011–6.CrossRefGoogle Scholar
  10. 10.
    Harrison DE. Long-term erythropoietic repopulating ability of old, young and fetal stem cells. J Exp Med. 1983;157:1496–504.PubMedCrossRefGoogle Scholar
  11. 11.
    Dolle ME, Giese H, Hopkins CL, Martus HJ, Hausdorff JM, Vijg J. Rapid accumulation of genome rearrangments in liver but not in brain of old mice. Nat Genet. 1997;4:431–4.CrossRefGoogle Scholar
  12. 12.
    Dolle ME, Snyder WK, Gossen JA, Lohman PH, Vijg J. Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine. Proc Natl Acad Sci USA. 2000;15:8403–8.CrossRefGoogle Scholar
  13. 13.
    Murphy KM, Travers P, Walport M. Janeway’s immunobiology, 7th ed. New York: Garland Science, Taylor and Francis Group; 2008Google Scholar
  14. 14.
    Silverman N, Maniatis T. NFkB signaling pathways in mammalian and insect innate immunity. Genes Dev. 2001;15:2321–42.PubMedCrossRefGoogle Scholar
  15. 15.
    Zerofsky M, Harel E, Silverman N, Tatar M. Aging of the innate immune response in drosophila melanogaster. Aging Cell. 2005;2:103–8.CrossRefGoogle Scholar
  16. 16.
    Van Duin D, Shaw A. Toll-like receptors in older adults. J Am Geriatr Soc. 2007;9:1438–44.CrossRefGoogle Scholar
  17. 17.
    Agrawal A, Agrawal S, Gupta S. Dendritic cells in human aging. Exp Gerontol. 2007;42:421–26.PubMedCrossRefGoogle Scholar
  18. 18.
    Shodell M, Siegal FP. Circulating, interferon-producing plasmacytoid dendritic cells decline during human ageing. Scand J Immunol. 2002;5:518–21.CrossRefGoogle Scholar
  19. 19.
    Fujihashi K, McGhee JR. Mucosal immunity and tolerance in the elderly. Mech Ageing Dev. 2004;12:889–98.CrossRefGoogle Scholar
  20. 20.
    Zavala WD, Cavicchia JC. Deterioration of the langerhans cell network of the human gingival epithelium with aging. Arch Oral Biol. 2006;51:1150–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Varas A, Sacedon R, Hernandez-Lopez C, et al. Age-dependent changes in thymic macrophages and dendritic cells. Microsc Res Tech. 2003;62:501–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Schuurhuis DH, Fu N, Ossendorp F, Melief CJM. Ins and outs of dendritic cells. Int Arch Allergy Immunol. 2006;140:53–72.PubMedCrossRefGoogle Scholar
  23. 23.
    Dubsky P, Ueno H, Piqueras B, Connoly H, Bachereau J, Palucka AK. Human dendritic cell subsets for vaccination. J Clin Immunol. 2005;25:551–72.PubMedCrossRefGoogle Scholar
  24. 24.
    Uyemura K, Castle SC, Makinodan T. The frail elderly: role of dendritic cells in the susceptibility of infection. Mech Ageing Dev. 2002;8:955–62.CrossRefGoogle Scholar
  25. 25.
    Kang YJ, Yang SJ, Park G, et al. A novel function of interleukin-10 promoting self-renewal of hematopoietic stem cells. Stem Cells. 2007;7:1814–22.CrossRefGoogle Scholar
  26. 26.
    Bottino C, Moretta L, Moretta A. NK cell activating receptors and tumor recognition in humans. Curr Top Microbiol Immunol. 2006;298:175–82.PubMedCrossRefGoogle Scholar
  27. 27.
    Ogata K, An E, Shioi Y, et al. Association between natural killer cell activity and infection in immunologically normal elderly people. Clin Exp Immunol. 2001;124:392–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhang Y, Wallace DL, de Lara CM, et al. In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infections. Immunology. 2007;2:258–65.CrossRefGoogle Scholar
  29. 29.
    Mariani E, Meneghetti A, Neri S, et al. Chemokine production by natural killer cells from nonagenarians. Eur J Immunol. 2002;32:1524–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Gomez CR, Acuna-Castillo C, Nishimura S, et al. Serum from aged F344 rats conditions the activation of young macrophages. Mech Ageing Dev. 2006;3:257–63.CrossRefGoogle Scholar
  31. 31.
    Fulop T, Larbi A, Douziech N, et al. Signal transduction and functional changes in neutrophils with aging. Aging Cell. 2005;4:217–26.CrossRefGoogle Scholar
  32. 32.
    Plowden J, Renshaw-Hoelscher M, Engleman C, Katz J, Sambhara S, et al. Innate immunity in aging: impact on macrophage function. Aging Cell. 2004;4:161–7.CrossRefGoogle Scholar
  33. 33.
    Herrero C, Marques L, Celada A. IFN-gamma-dependent transcription of MCH class II IA is impaired in macrophages from aged mice. J Clin Invest. 2001;4:485–93.CrossRefGoogle Scholar
  34. 34.
    Aspinall R, Andrew D. Thymic involution in aging. J Clin Immunol. 2000;4:250–6.CrossRefGoogle Scholar
  35. 35.
    Pawelec G, Tehbein A, Haehnel K, Merl A, Adibzadeh M. Human T-cell clones in long-term culture as a model of immunosenescence. Immunol Rev. 1997;160:31–42.PubMedCrossRefGoogle Scholar
  36. 36.
    Murasko DM, Weiner P, Kaye D. Decline in mitogen induced proliferation of lymphocytes with increasing age. Clin Exp Immunol. 1987;70:440–8.PubMedGoogle Scholar
  37. 37.
    Hobbs MV, Weigle WO, Noonan DJ, et al. Patterns of cytokine gene expression by CD4+ T cells from young and old mice. J Immunol. 1993;150:3602–14.PubMedGoogle Scholar
  38. 38.
    Jackola DR, Ruger JK, Miller RA. Age-associated changes in human T cell phenotype and function. Aging. 1994;6:25–34.PubMedGoogle Scholar
  39. 39.
    Enwerda CR, Handwerger BS, Fox BS. Aged T cells are hyporesponsive to costimulation mediated by CD28. J Immunol. 1994;152:3740–7.Google Scholar
  40. 40.
    Nociari MM, Telford W, Russo C. Postthymic development of CD28-CD8+ T cell subset: Age associated expansion and shift from emeory to anive phenotype. J Immunol. 1999;3327–35Google Scholar
  41. 41.
    Quadri RA, Plastre O, Phelouzat MA, Arbogast A, Proust JJ. Age-related tyrosine-specific protein phosphorylation defect in human T lymphocytes activated through CD3, CD4, CD8 or the IL-2 receptor. Mech Ageing Dev. 1996;88:125–38.PubMedCrossRefGoogle Scholar
  42. 42.
    Engwerda CR, Fox BS, Handwerger BS. Cytokine production by T lymphocytes from young and aged mice. J Immunol. 1996;156:3621–30.PubMedGoogle Scholar
  43. 43.
    Effros RB. Long-term immunological memory against viruses. Mech Ageing Dev. 2000;121:161–71.PubMedCrossRefGoogle Scholar
  44. 44.
    Murasko DM, Bernstein ED, Gardner EM, et al. Role of humoral and cell-mediated immunity in protection from influenza disease after immunization of healthy elderly. Exp Gerontol. 2002;37:427–39.PubMedCrossRefGoogle Scholar
  45. 45.
    Effros RB. Role of T lymphocyte replicative senescence in vaccine efficacy. Vaccine. 2007;25:599–604.PubMedCrossRefGoogle Scholar
  46. 46.
    Rytel MW. Effect of age on viral infections: possible role of interferon. J Am Geriatr. 1987;35:1092–99.Google Scholar
  47. 47.
    Maus MV, Kovacs B, Kwok WW, et al. Extensive replicative capacity of human central memory T cells. J Immunol. 2004;11:6675–83.Google Scholar
  48. 48.
    Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A. Human immunosenescence: is it infectious? Immunol Rev. 2005;205:257–68.PubMedCrossRefGoogle Scholar
  49. 49.
    Saule P, Trauet J, Dutriez V, Dessaint JP, Labalette M. Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment. Mech Ageing Dev. 2006;3:274–81.CrossRefGoogle Scholar
  50. 50.
    Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med. 1998;188:287–96.PubMedCrossRefGoogle Scholar
  51. 51.
    Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G. Ex vivo isolation and characterization of CD4+CD25+ T cells with regulatory properties from human blood. J Exp Med. 2001;193:1303–10.PubMedCrossRefGoogle Scholar
  52. 52.
    Jonuleir H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH. Identification and functional characterization of human CD4+CD25+ T cells with regulatory properties isolated from peripheral blood. J Exp Med. 2001;193:1285–94.CrossRefGoogle Scholar
  53. 53.
    Lages CS, Suffia I, Velilla PA, et al. Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J Immunol. 2008;181:1835–48.PubMedGoogle Scholar
  54. 54.
    Song H, Price PW, Cerny J. Age-related changes in antibody repertoire: contributions from T cells. Immunol Rev. 1997;160:55–62.PubMedCrossRefGoogle Scholar
  55. 55.
    Haynes L, Eaton SM, Burns EM, Randall TD, Swain SL. CD4 T cell memory derived from young naïve cells functions well into old age, but memory generated from aged naïve cells functions poorly. Proc Natl Acad Aci U S A. 2003;100:15053–8.CrossRefGoogle Scholar
  56. 56.
    Engwerda CR, Handwerger BS, Fox BS. Aged T cells are hyporesponsive to costimulation mediated by CD28. J Immunol. 1994;152:3740–7.PubMedGoogle Scholar
  57. 57.
    Haynes L, Linton PJ, Eaton SM, Tonkonogy SL, Swain SL. Interleukin 2, but not other common gamma chain binding cytokines, can reverse the defect in generation of CD4 effector T cells from naïve T cells of aged mice. J Exp Med. 1999;190:1013–24.PubMedCrossRefGoogle Scholar
  58. 58.
    Zheng B, Han S, Takahashi Y, Kelsoe G. Immunosenescence and germinal center reaction. Immunol Rev. 1997;160:63–77.PubMedCrossRefGoogle Scholar
  59. 59.
    Kilinman NR, Kline GH. The B-cell biology of aging. Immunol Rev. 1997;160:103–14.CrossRefGoogle Scholar
  60. 60.
    Goidl EA, Engle J, Chen HX, Schulze DH. Hybridomas reactive with TNP from aged mice are cross-reactive and display restricted VH and VL diversity. Aging Immunol Inf Dis. 1994;5:259–70.Google Scholar
  61. 61.
    Franceschi C, Monti D, Sansoni P, Cossarizza A. The immunology of exceptional individuals: the lesson of centenarians. Immunol Today. 1995;16:12–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Weksler ME. Changes in the B-cell repertoire with age. Vaccine. 2000;18:1624–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Kaminski DA, Stavnezer J. Antibody class switching: uncoupling S region accessibility from transcription. Trends Gent. 2004;20:337–40.CrossRefGoogle Scholar
  64. 64.
    Jacobson C, Strausbaugh LJ. Incidence and impact of infection in a nursing home care unit. Am J Infect Control. 1990;18:151–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Joseph ME, Sublett KL, Katz AL. Septic arthritis in the geriatric population. J Okla State Med Assoc. 1989;12:622–5.Google Scholar
  66. 66.
    Saketkoo L, Espinoza LR. Impact of biologic agents on infectious diseases. Infect Dis Clin North Am. 2006;20:931–61.PubMedCrossRefGoogle Scholar
  67. 67.
    Marculescu CE, Cantey JR. Polymicrobial prosthetic joint infections: risk factors and outcome. Clin Orthop Relat Res. 2008;466:1397–404.PubMedCrossRefGoogle Scholar
  68. 68.
    Hsieh PH, Lee MS, Hsuk Y, et al. gram-negative prosthetic joint infections: risk factors and outcome of treatment. Clin Infect Dis. 2009;49:1036–43.PubMedCrossRefGoogle Scholar
  69. 69.
    Yoskikawa TT. Tuberlulosis in aging adults. J Am Geriatr Soc. 1992;40:178–87.Google Scholar
  70. 70.
    Perez-Guzman C, Vargas MH, Torres-Cruz A, et al. Does aging modify pulmonary tuberculosis? A meta analytical review. Chest. 1999;116:961–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Evanchick CC, Davis DE, Harrington TM. Tuberculosis of peripheral joints: an often missed diagnosis. J Rheumatol. 1986;13:187–9.PubMedGoogle Scholar
  72. 72.
    Tuli SM. Results of treatment of spinal tuberculosis by “middle-path” regime. J Bone Joint Surg Br. 1975;57:13–23.PubMedGoogle Scholar
  73. 73.
    Koch S, Larbi A, Ozcelik D, et al. Cytomegalovirus infection: a driving force in human T cell immunosenescence. Ann NY Acad Sci. 2007;1114:23–35.PubMedCrossRefGoogle Scholar
  74. 74.
    Wikby A, Ferguson F, Forsey R, et al. An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagerian humans. J Gerontol A Biol Sci. 2005;60:556–65.Google Scholar
  75. 75.
    Blair JE, Mayer AP, Currier J, Files JA, Wu Q. Coccidioidomycosis in elderly persons. Clin Infec Dis. 2008;47:1513–8.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.LSU Health Sciences CenterNew OrleansUSA

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