Identifying correlates of immunity or susceptibility to disease promotes understanding of pathogenesis and development of diagnostic tools, treatments, and vaccines. There is evidence that type 1 cytokine responses are associated with protection against tuberculosis, and suppression of type 1, or switching to type 2 responses, with susceptibility, but this has not been studied prospectively. We studied a cohort of 631 HIV-1-infected Ugandan adults. At enrollment we performed whole blood cultures for type 1 (interferon [IFN]-gamma, interleukin [IL]-2) and type 2/immunosuppressive (IL-5, IL-10) responses to mycobacterial antigens (purified protein derivative [PPD] and culture filtrate proteins [CFP]). The incidence of tuberculosis was not associated with IFN-gamma responses, but was higher among participants with IL-2 responses (adjusted rate ratios [RR]: PPD 3.48; CFP 3.99; P < 0.001). For tuberculin skin test-positive participants, high incidence was also associated with an IL-10 response to PPD (adjusted RR 6.24, P = 0.03); for those with a BCG scar, high incidence was associated with positive IL-5 responses (adjusted RRs: PPD 3.64, P = 0.006; CFP 3.44, P = 0.04). The association with IL-2 production may reflect a response to tuberculous infection or to activating disease; the associations with IL-10 and IL-5 are in keeping with the expected role of immunosuppressive or type 2 cytokines.
HIV-positive patients with pleural tuberculosis show elevated production of IFN-gamma, for which CD8+ T cells may be a major source. Mycobacterium tuberculosis can proliferate despite high levels of pro-inflammatory cytokines.
The systematic nomination and questioning of a panel of experts provides a foundational and educational resource to assist in clarification of clinical ethics, philosophy, and research development in the emerging field of naturopathic oncology.
The ubiquitous and detrimental disease of breast cancer requires continual research into new and alternative forms of treatment and prevention. The emerging field of epigenetics is beginning to unfold an array of contemporary approaches to reduce the risk and improve the clinical approach to breast cancer. The information contained in this non-systematic review highlights and expands on the estrogen-based model of breast cancer epigenetics to provide an overview of epigenetic alterations induced by nutrition and environmental exposure. The majority of evidence suggests that various sources of excess estrogen correlate to future breast cancer development. In addition, maternal macro- and micronutrient balance appear to play a role in genomic regulation, and preliminary data suggest that specific superfoods, such as blueberries, have a protective epigenetic effect. Identifying the influence of environmental toxicants, hormonal exposure, maternal nutrition, and maternal disease on fetal epigenetics may have potential for development of new therapeutic approaches for the prevention of breast cancer.
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