The effect of cardiovascular drugs on pro-inflammatory cytokine secretion and natural killer activity of peripheral blood mononuclear cells of patients with chronic heart failure in vitro.
Recent studies have shown that patients with heart failure over-express pro-inflammatory cytokines which enhance natural killer (NK) activity and negatively influence contractility and contribute to the remodeling of myocardium. The question is that how cardiovascular drugs influence on the cytokines of Peripheral Blood Mononuclear Cells (PBMCs) in Chronic Heart Failure (CHF). To study the effect of cardiovascular drugs on PBMCs-cytokines and NK activity of CHF patients. PBMCs of CHF patients/normal controls collected by Ficoll-paque density centrifugation. NK activity against K562 target cell was measured with MTT colorimetric assay. PBMCs were cultivated in RPMI/FCS, stimulated with phytohaemaglutinin (PHA). Tumor necrosis factor (TNF)-alpha interleukin (IL)-6, IL-2 and IL-1beta of culture supernatants after 24 h incubation with/without furosemide, captopril and digoxin were measured with sandwitch ELISA. Patients had higher NK activity than controls (56.9% +/- 1.6 vs 50.9% +/- 1.2, p < 0.05). NK activity of patients who already consumed Captopril/Furosemide didn't show difference with controls. Captopril (3, 1, 0.3 microg mL(-1)) and Furosemide (5, 2.5, 1.25 microg mL(-1)) caused a dose dependent inhibition in TNF-alpha compared with control (329 +/- 23, 427 +/- 15, 519 +/- 19 and 343 +/- 19, 430 +/- 14, respectively vs. 562 +/- 24 pg mL(-1) p < 0.05). Furosemide caused a dose dependent decrease in IL-6 (421 +/- 31, 534 +/- 33 vs. 662 +/- 41 pg mL(-1) p < 0.05). Captopril and Furosemide didn't show any significant effect on IL-1beta/IL-2. Digoxin had no significant effect on PBMCs-cytokines. These data suggest that the immunomodulatory effects of Captopril and Furosemide may contribute to their beneficial and no long-term adverse effects on PBMCs.
Sheikhi
Abdolkarim
A
Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Jaberi
Yahya
Y
Esmaeilzadeh
Abdolreza
A
Khani
Mohammad
M
Moosaeefard
Mehdi
M
Shafaqatian
Mostafa
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005665:Furosemide / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male
D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; D004232:Diuretics; D018836:Inflammation Mediators; D005665:Furosemide; D002216:Captopril