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Title: The effect of diuretics and combined drugs (diuretic + ACEI) on the immunological activity of murine macrophages
Abstract:
Introduction: Hypertension is a disease associated with chronic inflammation involving activated macrophages. Antihypertensive drugs (for example, angiotensin-converting enzyme inhibitors - ACEIs) used to treat hypertension have immunomodulatory properties. On the other hand, the effects of diuretics and combined drugs (diuretics + ACEIs) on the immune system remained unclear. Therefore, it was reasonable to investigate the effect of diuretics and combined drugs (ACEI + diuretic) on the cellular response (contact hypersensitivity), the production of reactive oxygen species (ROI) and nitric oxide (NO) by macrophages, as well as anti-inflammatory and pro-inflammatory cytokines, as well as the humoral response. The review article describes the immunomodulatory functions of diuretics, in which the impact on the immune response of this group of drugs was reported both in patients suffering from hypertension and in experimental conditions including animal models and cell line studies. Objective: The aim of this research project was to comprehensively determine the unexplored effect of diuretics and combined drugs (ACEI + diuretic) on the immunological activity of murine macrophages as cells performing important functions in innate immunity (phagocytosis) and adaptive immunity (both humoral and cellular response). Methods: CBA mice were intraperitoneally administered captopril (5 mg/k ; g) and/or hydrochlorothiazide (10 mg/kg) or furosemide (5 mg/kg) for 8 days. On the third day, mice were administered mineral oil intraperitoneally, and macrophages were collected 5 days later. Collected peritoneal macrophages were assessed for their ability to produce cytokines by ELISA, and the expression of surface markers was analyzed cytometrically. Additionally, macrophages were incubated with sheep red blood cells (SRBCs) and administered to naive mice to assess their ability to induce a humoral immune response. However, the activity of hapten-labeled macrophages was assessed in the mechanisms of cellular immunity. Results: The presented results showed that diuretics administered alone or with captopril increased the generation of reactive oxygen species and reduced the formation of nitric oxide by macrophages. Additionally, the tested drugs inhibited the secretion of IL-12p40. Diuretics and combined drugs reduced the activity of contact hypersensitivity (both the induction and effector phases). The tested drugs increased the expression of surface markers important for phagocytosis and antigen presentation. Macrophages from mice treated with captopril combined with diuretics after SRBC phagocytosis and adoptive transfer increased the secretion of antigen-specific antibodies by recipient B cells, whereas macrophages from mice treated with hydrochlorothiazide alone as well ; as furosemide plus captopril increased the number of antigen-specific B cells. The tested drugs changed the secretory profile of macrophages in favor of anti-inflammatory cytokines. The vast majority of diuretics modulated the immune response, changing it in favor of an anti-inflammatory response, but these effects may vary depending on the drug. This topic is important in medical practice regarding the treatment of patients with comorbidities of chronic pathogenesis inflammation, including hypertension or chronic heart failure. Patients with metabolic syndrome, allergies or autoimmune diseases benefit from the anti-inflammatory effect due to excessive stimulation of their immune system. However, in the geriatric population, it is important to find the right anti-inflammatory and pro-inflammatory balance to avoid increased suppression of the immune response, which may result in an increased risk of serious infections that may occur due to the weakening of the immune system function with age. Conclusions: Our studies show that the tested drugs modulate the cellular and humoral response by influencing the function of macrophages, which is important in assessing the safety of antihypertensive therapy. Moreover, together with the conclusions resulting from the analysis of literature data in the review article, the conclusions presented in this dissertation facilitate the selection ; of a diuretic depending on the patient's immunological situation.
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Rada Dyscypliny Nauki medyczne
Promoter:
Marcinkiewicz, Janusz ; Nazimek, Katarzyna
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Last modified:
Dec 18, 2024
In our library since:
Oct 28, 2024
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4
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All available object's versions:
http://dl.cm-uj.krakow.pl:8080/publication/5169
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| Edition name | Date |
|---|---|
| ZB-140539 | Dec 18, 2024 |
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