Increase of CXC chemokine CXCL10 and CC chemokine CCL2 serum levels in normal ageing.

No study has evaluated contemporaneously serum CXC and CC chemokines changes in normal ageing. Serum levels of CXCL10 (sCXCL10) (CXC) and CCL2 (sCCL2) (CC) prototype chemokines have been measured in 164 healthy subjects, from 10 to 79 years of age (82 males/82 females). By simple regression analysis, sCXCL10 and sCCL2 were significantly related with increasing age (r=0.32, p<0.001; r=0.31, p<0.0001, respectively), and with each other (r=0.30, p=0.0004). In a multiple linear regression model, only age and sCCL2 were significantly related to sCXCL10 levels (p<0.001); age and sCXCL10 were significantly related to sCCL2 levels (p<0.001). Subjects with high sCXCL10 levels (>150 pg/ml) were not significantly associated with those with high sCCL2 levels (>559 pg/ml). This study, performed in healthy subjects on an age gradient, demonstrates an increase of sCXCL10 and sCCL2 with advancing age; the differential increase of sCXCL10 or sCCL2 may reflect a general shift towards Th1 or Th2 cytokines pattern, respectively.

[1]  M. Rotondi,et al.  High levels of circulating CXC chemokine ligand 10 are associated with chronic autoimmune thyroiditis and hypothyroidism. , 2004, The Journal of clinical endocrinology and metabolism.

[2]  Luca Chiovato,et al.  Expression of IP-10/CXCL10 and MIG/CXCL9 in the thyroid and increased levels of IP-10/CXCL10 in the serum of patients with recent-onset Graves' disease. , 2002, The American journal of pathology.

[3]  N. Holbrook,et al.  Aging--causes and defenses. , 1993, Annual review of medicine.

[4]  G. Shearer,et al.  Th1/Th2 changes in aging. , 1997, Mechanisms of ageing and development.

[5]  F. Nicoletti,et al.  Serum concentrations of the interferon-γ-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease , 2002, Diabetologia.

[6]  Y. Ouchi,et al.  Increase in circulating levels of monocyte chemoattractant protein-1 with aging. , 1999, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[7]  A. Weetman,et al.  Detection and localization of chemokine gene expression in autoimmune thyroid disease , 2003, Clinical endocrinology.

[8]  M. Rotondi,et al.  Increase of interferon-gamma inducible alpha chemokine CXCL10 but not beta chemokine CCL2 serum levels in chronic autoimmune thyroiditis. , 2005, European journal of endocrinology.

[9]  C. Franceschi,et al.  The immune system in the elderly , 2004, Immunologic research.

[10]  R. Daynes,et al.  Altered regulation of IL-6 production with normal aging. Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative. , 1993, Journal of immunology.

[11]  H. Mcdevitt,et al.  Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. , 1995, Immunology today.

[12]  Chilosi,et al.  Progressive polarization towards a T helper/cytotoxic type‐1 cytokine pattern during age‐dependent maturation of the immune response inversely correlates with CD30 cell expression and serum concentration , 1999, Clinical and experimental immunology.

[13]  P. Marchetti,et al.  Anti‐CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves' disease , 2001, Clinical and experimental immunology.

[14]  D. Quaglino,et al.  The immune system in the elderly: I. Specific humoral immunity. , 1999, Immunologic research.

[15]  C. Franceschi,et al.  Inflamm‐aging: An Evolutionary Perspective on Immunosenescence , 2000 .

[16]  D. Quaglino,et al.  The immune system in the elderly: II. Specific cellular immunity. , 1999, Immunologic research.

[17]  W. Karpus,et al.  Differential CC chemokine-induced enhancement of T helper cell cytokine production. , 1997, Journal of immunology.

[18]  Haimin Xu,et al.  Increase of plasma IL-6 concentration with age in healthy subjects. , 1992, Life sciences.

[19]  L. Tsui,et al.  From naive to effector ‐ alterations with aging , 1997, Immunological reviews.

[20]  A. Zlotnik,et al.  Chemokines: a new classification system and their role in immunity. , 2000, Immunity.

[21]  C. Franceschi,et al.  Increased cytokine production in mononuclear cells of healthy elderly people , 1993, European journal of immunology.

[22]  C. Franceschi,et al.  Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians , 2001, Mechanisms of Ageing and Development.

[23]  E. Mariani,et al.  Age-associated changes in functional response to CXCR3 and CXCR5 chemokine receptors in human osteoblasts , 2004, Biogerontology.

[24]  H. Morita,et al.  Significance of the level of monocyte chemoattractant protein-1 in human atherosclerosis. , 2004, Circulation journal : official journal of the Japanese Circulation Society.

[25]  Richard A. Miller The Aging Immune System: Primer and Prospectus , 1996, Science.

[26]  S. S. Franceschini,et al.  Interferon-γ-Inducible α-Chemokine CXCL10 Involvement in Graves’ Ophthalmopathy: Modulation by Peroxisome Proliferator-Activated Receptor-γ Agonists , 2006 .

[27]  D. Pawlak,et al.  Possible New Role of Monocyte Chemoattractant Protein-1 in Hemodialysis Patients with Cardiovascular Disease , 2004, American Journal of Nephrology.

[28]  L. Rink,et al.  Altered cytokine production in the elderly , 1998, Mechanisms of Ageing and Development.

[29]  A. Luster,et al.  Chemokines--chemotactic cytokines that mediate inflammation. , 1998, The New England journal of medicine.

[30]  J. French,et al.  The incidence of thyroid disorders in the community: a twenty‐year follow‐up of the Whickham Survey , 1995, Clinical endocrinology.

[31]  A. Weetman Cellular immune responses in autoimmune thyroid disease , 2004, Clinical endocrinology.

[32]  K. Egashira Molecular Mechanisms Mediating Inflammation in Vascular Disease: Special Reference to Monocyte Chemoattractant Protein-1 , 2003, Hypertension.

[33]  R. Miller,et al.  Age-associated decline in IL-4 production by murine T lymphocytes in extended culture. , 1993, Cellular immunology.

[34]  E. Mariani,et al.  Chemokine production by peripheral blood mononuclear cells in elderly subjects , 2001, Mechanisms of Ageing and Development.

[35]  M. Baggiolini Chemokines and leukocyte traffic , 1998, Nature.

[36]  T. Kita,et al.  Altered Th1/Th2 commitment in human CD4+ T cells with ageing , 2000, Clinical and experimental immunology.

[37]  J. Myśliwska,et al.  Increase of interleukin 6 and decrease of interleukin 2 production during the ageing process are influenced by the health status , 1998, Mechanisms of Ageing and Development.

[38]  K. Chida,et al.  Decreased expression of Th2 type cytokine mRNA contributes to the lack of allergic bronchial inflammation in aged rats. , 1999, Journal of immunology.

[39]  S. Romagnani The Th1-Th2 paradigm in disease , 1996 .

[40]  F. Sánchez‐Madrid,et al.  Thyrocytes from autoimmune thyroid disorders produce the chemokines IP-10 and Mig and attract CXCR3+ lymphocytes. , 2001, The Journal of clinical endocrinology and metabolism.

[41]  S. Romagnani,et al.  The Th1/Th2 paradigm. , 1997, Immunology today.

[42]  M. Salvadori,et al.  High Pretransplant Serum Levels of CXCL10/IP‐10 Are Related to Increased Risk of Renal Allograft Failure , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[43]  S. Akira,et al.  Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Raftery,et al.  Pretransplantation levels of C-reactive protein predict all-cause and cardiovascular mortality, but not graft outcome, in kidney transplant recipients. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.