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[Action of ketotifen on the mitogen-evoked proliferative response of human mononuclear cells]
Abstract:
Ketotifen at low concentrations (5 and 50 microns) potentiated and at high ones (250 and 500 microM) blocked the proliferative response of human peripheral blood mononuclear cells ( NNC ) induced by PHA. The proliferative response was evaluated by 3H-thymidine incorporation into the cells. At doses inhibiting proliferative response to PHA ketotifen blocked both Con A-induced and Pokeweed mitogen-induced proliferations of MNC. At tested concentrations ketotifen inhibited and at the highest concentration (250 microM) blocked PHA-induced increase of protein synthesis in MNC evaluated by incorporation of 14C-L-leucine into the cells. The presented data showed that ketotifen acted not on the inductive step of the proliferative response but on the steps preceding the cell shift into S-phase.
Insights
Ketotifen, an anti-allergic drug, affects human peripheral blood mononuclear cell proliferation. Low doses enhance, while high doses inhibit cell growth and protein synthesis, impacting cell cycle progression.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Context:
- Human peripheral blood mononuclear cells (MNCs) are crucial for immune responses.
- Phytohemagglutinin (PHA) is a common mitogen used to stimulate MNC proliferation.
- Ketotifen is an antihistamine and mast cell stabilizer with potential immunomodulatory effects.
Purpose:
- To investigate the dose-dependent effects of ketotifen on human MNC proliferation and protein synthesis.
- To determine the specific stage of the cell cycle affected by ketotifen during mitogenic stimulation.
Summary:
- Ketotifen exhibits a biphasic effect on PHA-induced MNC proliferation: potentiation at low concentrations (5-50 µM) and inhibition at high concentrations (250-500 µM).
- High-dose ketotifen also inhibited Concanavalin A (Con A) and Pokeweed mitogen (PWM)-induced proliferation.
- Ketotifen inhibited PHA-induced protein synthesis and acted on cell cycle phases preceding DNA synthesis (S-phase).
Impact:
- These findings elucidate ketotifen's complex immunomodulatory mechanisms.
- Understanding ketotifen's impact on cell cycle progression is vital for its therapeutic applications.
- The study provides insights into ketotifen's potential as an immunomodulator beyond its anti-allergic properties.