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A peripheral circulating TH1 cytokine profile is inversely associated with prostate cancer risk in CLUE II.

ABSTRACT: TH1 cytokines, such as IFN? and TNF?, and potentially innate cytokines, such as IL6, can potentiate the immune response to tumor. Cytokines, such as IL1?, IL8, and IL10, may suppress anticancer immunity. Thus, we prospectively evaluated the association between peripheral-cytokine concentrations and prostate cancer.We conducted an age-race matched case-control study (268 pairs) of incident prostate cancer in CLUE-II. We measured plasma IFN?, IL10, IL12p70, IL1?, IL6, IL8, and TNF? concentrations using an ultrasensitive multiplex kit. ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression.The OR of prostate cancer decreased across quartiles of IFN? (highest vs. lowest quartiles: OR, 0.49; 95% CI, 0.30-0.81; Ptrend = 0.006), TNF? (OR, 0.56; 95% CI, 0.33-0.96; Ptrend = 0.01), and IL6 (OR, 0.46; 95% CI, 0.26-0.79; Ptrend = 0.007). Higher TNF? (OR, 0.28; 95% CI, 0.09-0.85; Ptrend = 0.01) and IL6 (OR, 0.20; 95% CI, 0.06-0.67; Ptrend = 0.003) concentrations were associated with lower Gleason sum ?7 disease risk. Other cytokines were not as clearly associated with risk.Men with a prediagnostic circulating TH1 profile and higher IL6 may have a lower risk of prostate cancer, including aggressive disease. Whether this profile reflects (i) an intraprostatic immune environment in benign tissue that protects against prostate cancer, (ii) the immune milieu in response to a prostate adenocarcinoma that inhibits tumor growth and detectability, and/or (iii) a systemic immune profile that mediates the influence of modifiable factors on risk, warrants additional study.Identifying specific inflammatory cytokines associated with prostate cancer may lead to improved prevention and treatment strategies.

SUBMITTER: Bhavsar NA

PROVIDER: S-EPMC4648294 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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A peripheral circulating TH1 cytokine profile is inversely associated with prostate cancer risk in CLUE II.

Bhavsar Nrupen A NA Bream Jay H JH Meeker Alan K AK Drake Charles G CG Peskoe Sarah B SB Dabitao Djeneba D De Marzo Angelo M AM Isaacs William B WB Platz Elizabeth A EA

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20140822 11

<h4>Background</h4>TH1 cytokines, such as IFNγ and TNFα, and potentially innate cytokines, such as IL6, can potentiate the immune response to tumor. Cytokines, such as IL1β, IL8, and IL10, may suppress anticancer immunity. Thus, we prospectively evaluated the association between peripheral-cytokine concentrations and prostate cancer.<h4>Methods</h4>We conducted an age-race matched case-control study (268 pairs) of incident prostate cancer in CLUE-II. We measured plasma IFNγ, IL10, IL12p70, IL1β, ...[more]

PMID: 25150281

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Project description:A major component of COVID-19 severe respiratory syndrome is the patient's immune response to the SARS-CoV-2 virus and the consequential multi-organ inflammatory response. Several studies suggested a potential role of CD4+ T cells in COVID-19 severe respiratory syndrome. We first hypothesized that there is a type 2 helper (Th2)/type 1 helper (Th1) imbalance in older age, male, asthma, smokers, and high ACE2 expression phenotype in the airway of non-infected patients. Next, we hypothesized that a Th2/Th1 imbalance may predict higher mortality in COVID-19 infected hospitalized patients with and without patient reported current asthma. We first analyzed publicly available gene expression from the sputum of 118 moderate-to-severe asthma patients and 21 healthy controls, and from nasal epithelium of 26 healthy current smokers and 21 healthy never smokers. Secondly, we profiled 288 new serum proteomics samples measured at admission from patients hospitalized within the Mount Sinai Health System with positive SARS-CoV-2 infection. We first computed Th1 and Th2 pathway enrichment scores by gene set variation analysis and then compared the differences in Th2 and Th1 pathway scores between patients that died compared to those that survived, by linear regression. The level of Th2/Th1 imbalance, as determined by the enrichment score, was associated with age, sex, and ACE2 expression in sputum, and with active smoking status in nasal epithelium (p < 0.05). Th2/Th1 imbalance at hospital admission in sera of patients was not significantly associated with death from COVID-19 (p = 0.11), unless evaluated in the asthmatic strata (p = 0.01). Using a similar approach we also observed a higher Th17/Th1 cytokine imbalance in all deceased patients compared to those that survived (p < 0.001), as well as in the asthmatic strata only (p < 0.01). Th2/Th1 imbalance is higher in the sera of asthma patients at admission that do not survive COVID-19, suggesting that the Th2/Th1 interplay may affect patient outcomes in SARS-CoV2 infection. In addition, we report that Th17/Th1 imbalance is increased in all patients that die of COVID-19.

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A peripheral circulating TH1 cytokine profile is inversely associated with prostate cancer risk in CLUE II.

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A peripheral circulating TH1 cytokine profile is inversely associated with prostate cancer risk in CLUE II.

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