Sildenafil Citrate Influences Production of TNF-<i>α</i> in Healthy Men Lymphocytes

Zych, Michał; Roszczyk, Aleksander; Kniotek, Monika; Kaleta, Beata; Zagożdżon, Radosław

doi:10.1155/2019/8478750

Cited by 9 publications

(9 citation statements)

References 33 publications

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“…It was also reported that sildenafil reduced ionized calcium-binding adapter molecule 1 (Iba-1), IFN-γ, and IL-1β levels in an inflammatory demyelination model in INOS knockout mice [ 61 , 63 ]. We did not notice such a phenomenon concerning idNK cell cultures in the current research as well as in our previous research, SC did not influence the percentage of T lymphocytes producing IFN–γ in the PBMC cultures in healthy men [ 64 ].…”

Section: Discussionsupporting

confidence: 44%

Sildenafil Citrate Downregulates PDE5A mRNA Expression in Women with Recurrent Pregnancy Loss without Altering Angiogenic Factors—A Preliminary Study

Kniotek

Roszczyk

Zych

et al. 2021

JCM

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In our previous study, we showed that sildenafil citrate (SC), a selective PDE5A blocker, modulated NK cell activity in patients with recurrent pregnancy loss, which correlated with positive pregnancy outcomes. It was found that NK cells had a pivotal role in decidualization, angiogenesis, spiral artery remodeling, and the regulation of trophoblast invasion. Thus, in the current study, we determined the effects of SC on angiogenic factor expression and production, as well as idNK cell activity in the presence of nitric synthase blocker L-NMMA. Methods: NK cells (CD56+) were isolated from the peripheral blood of 15 patients and 15 fertile women on MACS columns and cultured in transformation media containing IL-15, TGF-β, and AZA—a methylation agent—for 7 days in hypoxia (94% N2, 1% O2, 5% CO2). Cultures were set up in four variants: (1) with SC, (2) without SC, (3) with NO, a synthase blocker, and (4) with SC and NO synthase blocker. NK cell activity was determined after 7 days of culturing as CD107a expression after an additional 4h of stimulation with K562 erythroleukemia cells. The expression of the PDE5A, VEGF-A, PIGF, IL-8, and RENBP genes was determined with quantitative real-time PCR (qRT-PCR) using TaqMan probes and ELISA was used to measure the concentrations of VEGF-A, PLGF, IL-8, Ang-I, Ang-II, IFN–γ proteins in culture supernatants after SC supplementation. Results: SC downregulated PDE5A expression and had no effect on other studied angiogenic factors. VEGF-A expression was increased in RPL patients compared with fertile women. Similarly, VEGF production was enhanced in RPL patients’ supernatants and SC increased the concentration of PIGF in culture supernatants. SC did not affect the expression or concentration of other studied factors, nor idNK cell activity, regardless of NO synthase blockade.

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Section: Discussionsupporting

confidence: 44%

Sildenafil Citrate Downregulates PDE5A mRNA Expression in Women with Recurrent Pregnancy Loss without Altering Angiogenic Factors—A Preliminary Study

Kniotek

Roszczyk

Zych

et al. 2021

JCM

Self Cite

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“…Isolated mouse splenocytes without red blood cells or tumor infiltrating lymphocytes (TILs) were stimulated in the presence of 50 ng/ml Phorbol 12-Myristate 13-acetate (PMA) (Sigma-Aldrich, St. Louis, MO) and 2 µM Ionomycin (Sigma-Aldrich), and treated with BD Golgi Stop (BD Biosciences, San Jose, CA) for 6 h at 37 °C in a humidified atmosphere of 5% CO 2 13 , 40 . After the culture, the cells were stained with fluorescent dye and monoclonal antibodies (mAbs): Zombie Aqua, CD3 (BV521), and CD8 (APC/Fire) mAbs (BioLegend, San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

Dysfunction of CD8 + PD-1 + T cells in type 2 diabetes caused by the impairment of metabolism-immune axis

Nojima

Eikawa

Tomonobu

et al. 2020

Sci Rep

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The metabolic changes and dysfunction in CD8 + T cells may be involved in tumor progression and susceptibility to virus infection in type 2 diabetes (T2D). In C57BL/6JJcl mice fed with high fat-high sucrose chow (HFS), multifunctionality of CD8 + splenic and tumor-infiltrating lymphocytes (TILs) was impaired and associated with enhanced tumor growth, which were inhibited by metformin. In CD8 + splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin. In the patients with T2D (DM), multifunctionality of circulating CD8 + PD-1 + T cells stimulated with PMA/ionomycin as well as with HLA-A*24:02 CMV peptide was dampened, while metformin recovered multifunctionality. Both glycolysis and basal respiration were reduced in DM, and glycolysis was increased by metformin. The disturbance of the link between metabolism and immune function in CD8 + PD-1 + T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity.

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Section: Discussionmentioning

confidence: 99%

“…It binds to the cGMP site, reduces the content of TNF-α, and shows a tendency to decrease IFN-γ. 23 According to the research carried out by Elbardisy, 24 certain therapeutic effects can be achieved by intranasal application of tadalafil, such as significantly reducing the content of inflammatory factors in serum of subjects, reducing inflammation and oxidative stress, and alleviating various biochemical indicators of patients with metabolic diseases. 25 It is shown in our study results that TNF-a, CRP and IL-6 in the experimental group are significantly lower than those in the control group after treatment, with statistically significant differences (TNF-a, p=0.01, CRP, p=0.00, IL-6, p=0.03).…”

Section: A H E a D O F P R I N Tmentioning

confidence: 99%

Effect of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with erectile dysfunction

Du¹,

Jia²,

Xue³

et al. 2021

Pak J Med Sci

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Objective: To evaluate the effect and clinical significance of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with Erectile dysfunction (ED). Methods: Eighty patients with hyperlipidemia complicated with ED who were treated at The Second Hospital of Hebei Medical University from January 2019 to June 2020 were selected. Using a completely randomized design experimental method, these 80 patients were randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. The control group was treated with a single drug, atorvastatin calcium, while the experimental group was given tadalafil orally on the basis of the control group for 3 months. Changes in the levels of inflammatory factors such as IL-6, TNF and CRP, adverse drug reactions, changes in hemodynamic indicators such as HSV, LSV, PSV, HCT and ESR before and after treatment, as well as changes in sexual function after treatment were compared and analyzed between the two groups. Results: TNF-a, CRP and IL-6 in the experimental group were significantly lower than those in the control group after treatment, with statistically significant differences (p<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (p=0.18). After treatment, hemodynamic indexes and sexual function indexes of the experimental group were significantly improved compared with those in the control group, with statistically significant differences (p<0.05). Conclusion: A significant improvement effect can be achieved by tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with ED. At the same time, the combination of the two has synergism on inflammatory factors and blood rheology, and the incidence of adverse reactions is not significantly increased. Abbreviations: ED: Erectile dysfunction, PDE-5: Phosphodiesterase-5, IL-6: Interleukin- 6, CRP: C-reactionprotein, HSV: High shear viscosity, LSV: Low cut viscosity of whole blood, PSV: The plasma viscosity, HCT: Hematocrit, ESR: Erythrocyte sedimentation rate, IIEF-5: International Index of Erectile Function Questionnaire – 5, HMG-CoA: Hydroxy-methylglutaryl coenzyme A, cGMP: cyclic Guanosinc monophosphate, TNF-α: Tumor necrosis factor-α, IFN-γ: Interferon-γ, TC: Total cholesterol, TG: Triglycerides, HDL-C: High density lipoprotein cholesterol. doi: https://doi.org/10.12669/pjms.37.7.4257 How to cite this:Du L, Jia J, Xue W, Qi J. Effect of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with erectile dysfunction. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4257 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Sildenafil Citrate Influences Production of TNF-α in Healthy Men Lymphocytes

Cited by 9 publications

References 33 publications

Sildenafil Citrate Downregulates PDE5A mRNA Expression in Women with Recurrent Pregnancy Loss without Altering Angiogenic Factors—A Preliminary Study

Sildenafil Citrate Downregulates PDE5A mRNA Expression in Women with Recurrent Pregnancy Loss without Altering Angiogenic Factors—A Preliminary Study

Dysfunction of CD8 + PD-1 + T cells in type 2 diabetes caused by the impairment of metabolism-immune axis

Effect of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with erectile dysfunction

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