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Objective: Circulating levels of sex hormones vary with age. Moreover, there is emerging evidence supporting that sex hormones have an influence on the immune response of women. Here, we investigated age-associated levels of sex hormones and Mycobacterium tuberculosis (Mtb) specific cytokines response in women. Design: Using immunoassay methods, we have measured and compared secretion levels of E2, P4 and Mtb specific secretion of 11 cytokines including Granulocyte-macrophage colony-stimulating factor (GM-CSF), Interferon gamma (IFN-γ), Interleukin 1 beta (IL-1β), IL-10, IL-12 (p70), IL-2, IL-4, IL-5, IL-6, IL-8, and Tumor necrosis factor (TNF-α) in forty-two (42) HIV-negative females. Results: Estradiol (E2) and progesterone (P4) levels were significantly higher in younger women irrespective of their LTB status (p Mtb IL-8 specific response was significantly higher in women above 40 years old than in women under 40 years old. Conclusion: In premenopausal women, there is an increase in the pro-inflammatory cytokine IL-8 secretion in response to Mtb-antigen. This observation suggests an underlying link between the pro-inflammatory cytokine and age associated hormonal changes, which may have implications on the course of tuberculosis infection women.

Tuberculosis (TB) is an intracellular infection controlled the effective recruitment of effectors immune cells at infection site. In aged premenopausal or menopausal women, there is an increased pro-inflammatory cytokines secretion suggesting an underlying link between cytokines response and estrogen (E2) and progesterone (P4) levels. In this study we compared women aged 40 years old and above (premenopausal) and women aged below 40 years old with and without latent TB infection to determine the link between E2, P4 and cytokines response to Mycobacterium tuberculosis (M. tuberculosis) stimuli. E2 and P4 levels were significantly higher in women under 40 years old than in women above 40 years old irrespective their LTB status (p < [0.0001–0.05]). In women under 40 years old, E2 and P4 were found to correlate negatively and significantly with IL-8 response to M. tuberculosis antigens stimulation ((p < [0.001–0.01]). Furthermore, M. tuberculosis IL-8 specific response was significantly higher in women above 40 years old than women under 40 years old. This study demonstrates that women aging and the linked hormonal changes are associated with hence IL-8 response to M. tuberculosis antigen, which may have implications for the age-related susceptibility or resistance to active tuberculosis.

Tuberculosis (TB) is the leading cause of death due to an infectious agent, but only a small fraction of those infected develop the disease. Cytokines are involved in the mediation and regulation of immunity, and their secretion patterns may reflect the infection status. To increase our understanding of immune response to M. tuberculosis infection, we conducted a cross-sectional study investigating M. tuberculosis infection status and comparing the release profiles of cytokines GM-CSF, IFN-γ, IL-1β, IL-10, IL-12 (p70), IL-2, IL-4, IL-5, IL-6, IL-8, TNF-α, in community controls (CCs) and healthy healthcare workers (HCWs) highly exposed to TB. Among HCWs and CCs, the probability of latent M. tuberculosis (LTB+) infection was respectively 5.4 (p = 0.002) and 3.4 (p = 0.006) times higher in men than women. The odds ratio of LTB infection was 4 times higher among HCWs in direct contact with active TB patients than other HCW (p = 0.01). Whole blood supernatant cytokine responses to M. tuberculosis antigens showed differential pro-inflammatory responses between HCWs and CCs. CCsLTB− had higher IL-1β responses than HCWsLTB− (p = 0.002). HCWsLTB+ had significantly higher IL-8 responses to M. tuberculosis antigens than HCWsLTB− (p = 0.003) and CCsLTB− (p = 0.015). HCWsLTB+/− showed weak but positive TNF-α responses to M. tuberculosis antigen stimulation compared to CCsLTB+/− (p ≤ 0.015). Looking at T-helper (1 and 2) responses, HCWsLTB+ and CCsLTB+ had significantly higher IFN-γ and IL-2 responses compared to HCWsLTB− and CCsLTB− (p LTB+ and CCsLTB+ than in non-infected CCsLTB− (p M. tuberculosis antigen specific responses in HCWsLTB+ varied based on active TB exposure gradient. HCWsLTB+ who were highly exposed to active TB (≥3 hours per day) had significantly higher IFN-γ and IL-8 responses (p ≤ 0.02) than HCWs LTB+ not in direct contact with active TB patients. HCWsLTB+ working with active TB patients for 5 to 31 years had a significantly enhanced secretion of proinflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-12p70, TNF-α) compared to HCWsLTB− (p LTB+ than HCWsLTB−. In conclusion, LTBI individuals controlling the M. tuberculosis infection have an enhanced TB specific Th1-cytokines/proinflammatory response combined with selected Th2 type/anti-inflammatory cytokines induction.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.