The implication of pro-inflammatory cytokines in the impaired production of gonadal androgens by patients with pulmonary tuberculosis

Bini, Estela Isabel; D’Attilio, Luciano; Marquina‐Castillo, Brenda; Mata-Espinosa, Dulce; Díaz, Ariana; Márquez-Velasco, Ricardo; Ramos-Espinosa, Octavio; Gamboa‐Domínguez, Armando; Bay, María Luisa; Hernández-Pando, Rogelio

doi:10.1016/j.tube.2015.06.002

Cited by 26 publications

(18 citation statements)

References 32 publications

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“…M1 macrophages often increase production of inflammatory cytokines such as IL‐12 and IL‐1β, whereas M2 macrophages often produce the anti‐inflammatory cytokine IL‐10 and TGF‐β . It has been reported that IL‐1 and IL‐12 confer host resistance to Mtb , whereas IL‐10 and TGF‐β facilitate Mtb escape from immune attack . Nigou et al .…”

Section: Discussionmentioning

confidence: 99%

A single‐stranded DNA aptamer against mannose‐capped lipoarabinomannan enhances anti‐tuberculosis activity of macrophages through downregulation of lipid‐sensing nuclear receptor peroxisome proliferator‐activated receptor γ expression

Pan

Yan

Liu

et al. 2017

Microbiology and Immunology

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Mannose-capped lipoarabinomannan (ManLAM) is an immunomodulatory epitope of Mycobacterium tuberculosis (Mtb). An aptamer (ZXL1) that specifically binds to ManLAM from the virulent Mtb H37Rv strain was previously generated and it was found that ZXL1 functions as an antagonist, inhibiting the ManLAM-induced immunosuppression of DCs. In the present study, it was found that ZXL1 inhibits Mtb entry into murine macrophages and that ZXL1 enhances IL-1β and IL-12 mRNA expression and cytokine production in ManLAM-treated macrophages but decreases IL-10 production. Inducible nitric oxide synthase expression in macrophages was upregulated in the presence of ZXL1 after stimulation with ManLAM. ZXL1 was also found to inhibit expression of lipid-sensing nuclear receptor peroxisome proliferator-activated receptor γ (PPAR-γ). These results suggest that ZXL1 promotes anti-tuberculosis activity through downregulation of PPAR-γ expression, which may contribute to M1 macrophage polarization and Mtb killing by macrophages.

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Section: Discussionmentioning

confidence: 99%

A single‐stranded DNA aptamer against mannose‐capped lipoarabinomannan enhances anti‐tuberculosis activity of macrophages through downregulation of lipid‐sensing nuclear receptor peroxisome proliferator‐activated receptor γ expression

Pan

Yan

Liu

et al. 2017

Microbiology and Immunology

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“…However, obesity and consumption of fatty food are both associated with a breakdown in intestinal mucosal integrity that allows passage of gut bacteria into the systemic circulation - so called “metabolic endotoxaemia” [19–22]. The resulting chronic state of low grade inflammation, typified by the production of pro-inflammatory cytokines such as Il-1β, TNFα and IL-6, has been reported to impair testicular steroidogenesis in both animal and human interventional studies [23–25]. …”

Section: Introductionmentioning

confidence: 99%

Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men

Tremellen

McPhee

Pearce

2017

Basic Clin. Androl.

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BackgroundObesity is associated with both impaired testosterone production and a chronic state of low grade inflammation. Previously it was believed that this inflammation was mediated by a decline in the immunosuppressive action of testosterone. However, more recently an alternative hypothesis (GELDING theory) has suggested that inflammation originating from the passage of intestinal bacteria into the circulation (metabolic endotoxaemia) may actually be the cause of impaired testicular function in obese men. The aim of this study is to investigate if metabolic endotoxaemia, as quantified by serum Lipopolysaccharide Binding Protein (LBP), is associated with impaired testicular endocrine function.MethodsA total of 50 men aged between 21 and 50 years (mean 35.1 ± 6.8 years) were assessed for adiposity (BMI, waist circumference and % body fat using bio-impedance), inflammatory status (serum CRP, IL-1β, IL-6, TNFα and LBP) and testicular endocrine function (serum testosterone, estradiol, AMH, LH and FSH). Statistical analysis was performed using Pearson correlation analysis, with log transformation of data where appropriate, and multi-variate regression.ResultsOverall increasing adiposity (% body fat) was positively associated with metabolic endotoxaemia (LBP, r = 0.366, p = 0.009) and inflammation (CRP r = 0.531, p < 0.001; IL-6 r = 0.463, p = 0.001), while also being negatively correlated with serum testosterone (r = −0.403, p = 0.004). Serum testosterone levels were significantly negatively correlated with inflammation (CRP r = −0.471, p = 0.001; IL-6 r = −0.516, p < 0.001) and endotoxaemia (LBP) after adjusting for serum LH levels (p = −0.317, p = 0.03). Furthermore, serum IL-6 was negatively associated with AMH levels (r = −0.324, p = 0.023), with a negative trend between LBP and AMH also approaching significance (r = −0.267, p = 0.064).ConclusionsObesity and its associated metabolic endotoxaemia helps initiate a pro-inflammatory state characterised by raised serum IL-6 levels, which in turn is correlated with impairment of both Leydig (testosterone) and Sertoli cell function (AMH). These results open up the potential for new treatments of obesity related male hypogonadism that focus on preventing the endotoxaemia associated chronic inflammatory state.

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“…A few studies indicated that sex hormones (e.g., androgen and estrogen) can regulate SOCS gene expression in prostate [11] and breast [12] cancer cells. Although testosterone was demonstrated as a TB susceptibility factor in mice system [13], TB patients showed lower levels of testosterone and higher levels of IL-6, IFN-γ, and TGF-β [14]. Further studies are needed to determine whether the association of sex hormones with cytokines explains the gender-dependent differences of SOCS expression between healthy and TB subjects.…”

Section: Resultsmentioning

confidence: 99%

Suppressors of cytokine signaling in tuberculosis

Lee

Liu

et al. 2017

PLoS ONE

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Tuberculosis (TB), a global disease mainly infected by Mycobacterium tuberculosis, remains leading public health problem worldwide. Suppressors of cytokine signaling (SOCSs) play important roles in the protection against microbial infection. However, the relationship between members of the SOCS family and tuberculosis infection remains unclear. Using peripheral blood mononuclear cells, we investigated the mRNA expression profiles of SOCS subfamilies among active TB, latent tuberculosis infection (LTBI), and healthy individuals. Our results showed that active tuberculosis subjects had higher levels of SOCS-3 mRNA, lower expressions of SOCS-2, -4, -5, -6, -7, and cytokine-inducible SH2-containing protein-1 (CIS-1) mRNAs, but not SOCS-1 mRNA than healthy and LTBI subjects. In men, LTBI patients had lower SOCS-3 than healthy subjects, and active TB patients had lower levels of SOCS-4, -5, and CIS-1 mRNAs but higher levels of SOCS-3 mRNA than healthy subjects. In women, LTBI patients had lower SOCS-3 mRNA level than healthy subjects, and active TB patients had lower CIS-1 mRNA level than healthy subjects. In non-aged adults (< 65 years old), TB patients had higher SOCS-3 mRNA and lower levels of SOCS-2, -4, -5, -6, -7, and CIS-1 mRNAs; whereas, aged TB patients (≥ 65 years old) had lower levels of SOCS-5 and CIS-1 mRNAs. These data suggest that particular SOCS members and their correlative relationships allow discrimination of active TB from healthy and LTBI subjects.

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The implication of pro-inflammatory cytokines in the impaired production of gonadal androgens by patients with pulmonary tuberculosis

Cited by 26 publications

References 32 publications

A single‐stranded DNA aptamer against mannose‐capped lipoarabinomannan enhances anti‐tuberculosis activity of macrophages through downregulation of lipid‐sensing nuclear receptor peroxisome proliferator‐activated receptor γ expression

A single‐stranded DNA aptamer against mannose‐capped lipoarabinomannan enhances anti‐tuberculosis activity of macrophages through downregulation of lipid‐sensing nuclear receptor peroxisome proliferator‐activated receptor γ expression

Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men

Suppressors of cytokine signaling in tuberculosis

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