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Arzneimittelforschung 2011; 61(12): 734-741
DOI: 10.1055/s-0031-1300595
Antibiotics · Antimycotics · Antiparasitics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

Suppressive effects of peptide antibiotics against proliferation and cytokine production in mitogen-activated human peripheral-blood mononuclear cells

Masaki Maeda
1   Bohsei Pharmacy, Isehara, Kanagawa, Japan
,
Sachiko Tanaka
2   Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
,
Hitomi Ishizawa
2   Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
,
Yurie Nakamura
2   Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
,
Kenji Onda
2   Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
,
Toshihiko Hirano
2   Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
09 February 2012 (online)

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Abstract

Certain kinds of peptide antibiotics are suggested to have immunomodulatory effects; however, few studies have been carried out systemically to evaluate the antiproliferative effects of peptide antibiotics in human lymphoid cells. The suppressive efficacies of nine peptide antibiotics and seven non-antibiotic peptides against proliferation of human peripheral-blood mononuclear cells (PBMCs) stimulated with T cell mitogen were examined in vitro. Nigericin (CAS 28643-80-3), valinomycin (CAS 2001-95-8), gramicidin D (CAS 1405-97-6), and tyrothricin (CAS 1404-88-2) strongly inhibited the proliferation of concanavalin A-stimulated PBMCs with IC50 values of 0.15–11.2 ng/ml, while these antibiotics did not show cytotoxicity at 10 000 ng/ml. The IC50 value of the immunosuppressant cyclosporine (CAS 59865-13-3) was 5.2 ng/ml. Virginiamycin (CAS 11006-76-1) and gramicidin S (CAS 113-73-5) moderately inhibited PBMC-proliferation with IC50 values of 1000 and 1900 ng/ml, respectively. On the other hand, bacitracin (CAS 1405-87-4), capreomycin (CAS 11003-38-6), polymyxin B (1404-26-8), angiotensin II antipeptide (CAS 121379-63-3), angiotensin III antipeptide (CAS 133605-55-7), fibrinogen binding inhibitor peptide (CAS 89105-94-2), LH-RH (CAS 71447-49-9), pepstatin A (CAS 26305-03-3), oxytocin (CAS 50-56-6), and vasopressin (CAS 16679-58-6) showed little or no suppressive effect on PBMC-proliferation. Nigericin and valinomycin decreased the concentrations of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-10, and IL-17 in the culture medium with IC50 values less than 0.01ng/ml. Nigericin also decreased the concentrations of IL-4 and IL-6 with IC50 values of less than 1 ng/ml. The results show that peptide antibiotics such as nigericin and valinomycin efficiently suppress the production of several cytokines and proliferation in mitogen-stimulated human PBMCs.

Key words

Cell proliferation - Cytokine production - Human peripheral blood mononuclear cells - Peptide antibiotics - T cell mitogen
 

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