Abstract

BackgroundAging of the immune system, known as immunosenescence, is associated with profound changes in both innate and adaptive immune responses, resulting in increased susceptibility to infection and a decreased ability to respond to vaccination. The purpose of this study was to investigate the effect of age and menopause on the expression of 22 different cytokines/chemokines in both plasma and cervical lavage samples from female sex-worker cohort from Nairobi, Kenya (age range 20–65).ResultsCytokine/chemokine levels were measured using a Miliplex multiplex assay (Millipore). We found that age positively correlated with MCP-1 (p = 0.0002) and IP-10 (p = 0.03) systemic cytokine expression, and that women over 50 expressed the highest levels of these cytokines, but also had elevated expression of MIG (ANOVA p = 0.0096) and MIP-3β(ANOVA p = 0.0434). We also found that IL-8 (p = 0.047) and sCD40L (p = 0.01) systemic expression negatively correlated with age. Further, MIG (p = 0.0081) and MCP-1 (p = 0.0157) were present at higher levels in post-menopausal women suggesting a potential estrogen dependant systemic regulation of these cytokines. In cervical lavage samples, age did not directly correlate with the expression of any of the tested cytokines/chemokines, however sIL-2Rα (ANOVA p = 0.0170) and IL-15 (ANOVA p = 0.0251)were significantly higher in women over 50. Menopause was shown to have a more profound effect on cytokine expression in the cervical mucosa with MIG (p = 0.0256), MIP-3α (p = 0.0245), IL-1β (p = 0.0261), IL-6 (p = 0.0462), IL-8 (p = 0.007), IP-10 (p = 0.0357) and MCP-1 (p = 0.0427) all significantly under-expressed in post-menopausal women.ConclusionsThis study demonstrates that aging and menopause-associated hormonal changes are associated with significant changes in systemic and mucosal cytokine/chemokine expression, which may have implications for the age-related decline in the ability to fight against infections.

Highlights

  • Aging of the immune system, known as immunosenescence, is associated with profound changes in both innate and adaptive immune responses, resulting in increased susceptibility to infection and a decreased ability to respond to vaccination

  • Aging has been associated with higher number of T regulatory (Treg) cells [5,18,19,20,21], a decline in B cell production and humoral immunity [21,22,23,24], chronic immune activation [23,25,26] and a shift from Th1 [Interleukin (IL-)2, Interferon-gamma (IFN-γ)] to a Th2-like cytokine response (IL-4, IL-6, IL10) [26,27]

  • Because other sexually transmitted diseases can greatly influence the expression of cytokines/chemokines at the systemic and mucosal level, all participants who tested positive for the presence of bacterial vaginosis, Nisseria gonorrhoeae, and/or Chlamydia were excluded from the analysis (n = 26)

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Summary

Introduction

Aging of the immune system, known as immunosenescence, is associated with profound changes in both innate and adaptive immune responses, resulting in increased susceptibility to infection and a decreased ability to respond to vaccination. Aging has been associated with higher number of T regulatory (Treg) cells [5,18,19,20,21], a decline in B cell production and humoral immunity [21,22,23,24], chronic immune activation [23,25,26] and a shift from Th1 [Interleukin (IL-), Interferon-gamma (IFN-γ)] to a Th2-like cytokine response (IL-4, IL-6, IL10) [26,27] All these data suggest that the ability of an older individual to respond appropriately to an immunological challenge is compromised thorough variety of mechanisms

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