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Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F and IL-22 in PBMCs from
Pablo R G Cardoso1, Katherine A Matias1, Andrea T Dantas2
1Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Nucleus of Research in Immunomodulation and New Therapeutic Approaches Suely Galdino (Nupit SG), Federal University of Pernambuco (UFPE), Recife, Brazil.
Insights
Losartan effectively reduces inflammatory cytokines in Rheumatoid Arthritis (RA) patients with Systemic Arterial Hypertension (SAH). This antihypertensive may offer immunomodulatory benefits, particularly for patients in remission or with mild disease activity.
Area of Science:
- Immunology
- Cardiology
- Pharmacology
Background:
- Rheumatoid Arthritis (RA) is a chronic inflammatory condition affecting 1% of the global population.
- Approximately 70% of RA patients also have Systemic Arterial Hypertension (SAH).
- Inflammatory cytokines play a key role in RA pathogenesis and are linked to SAH.
Purpose of the Study:
- To investigate the potential immunomodulatory effects of antihypertensive drugs.
- To determine the optimal antihypertensive choice for RA patients with SAH.
Main Methods:
- Peripheral Blood Mononuclear Cells (PBMCs) from 16 RA patients were isolated and treated with Enalapril, Losartan, or Valsartan.
- Disease activity was assessed using the Clinical Disease Activity Index (CDAI) and Disease Activity Score (DAS28).
- Cytokine levels (IFN-γ, IL-6, IL-17F, IL-22) were quantified using ELISA.
Main Results:
- Losartan significantly reduced levels of IFN-γ, IL-6, IL-17F, and IL-22 in RA patients.
- Patients in remission or with mild RA (DAS28<3.2, CDAI<10) showed a better response to Losartan.
- Patients with moderate to severe RA exhibited a diminished response to Losartan's cytokine inhibition.
Conclusions:
- PBMCs from RA patients demonstrate responsiveness to Losartan's anti-inflammatory cytokine effects.
- Losartan appears to be a more effective immunomodulatory antihypertensive agent compared to Enalapril and Valsartan for RA patients with SAH.
- Losartan may be a preferred treatment option for managing both RA and SAH concurrently.
Background:
Rheumatoid Arthritis (RA) is a chronic and inflammatory disease that affects about 1% of the world's population. Almost 70% of RA patients have a cardiovascular disease such as Systemic Arterial Hypertension (SAH). Inflammatory cytokines are clearly involved in the pathogenesis of RA and correlated with SAH.
Objective:
It is necessary to understand whether the antihypertensive drugs have a dual effect as immunomodulators and which one is the best choice for RA SAH patients.
Methods:
Peripheral Blood Mononuclear Cells (PBMCs) from 16 RA patients were purified and stimulated or not stimulated with anti-CD3 and anti-CD28 mAB and were treated with Enalapril, Losartan and Valsartan at 100μM. Patients were evaluated for clinical and laboratory variables including measures of disease activity by Clinical Disease Activity Index (CDAI) and Disease Activity Score (DAS28). Cytokines were quantified by ELISA sandwich.
Results:
Losartan was able to reduce levels of IFN-γ (p = 0.0181), IL-6 (p = 0.0056), IL-17F (0.0046) and IL-22 (p = 0.0234) in RA patients. In addition, patients in remission and mild score (DAS28<3.2 and CDAI<10) had a better response to treatment. On the other hand, patients in moderate and severe activity had poor response to Losartan in cytokine inhibition.
Conclusion:
PBMCs from RA patients are responsive in inhibiting proinflammatory cytokines using Losartan better than Enalapril and Valsartan and it could be a better antihypertensive choice for patients with RA and systemic arterial hypertension treatment.
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