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Treatment with cyclosporin A does not affect macrophage procoagulant activity and plasminogen activator inhibitor in
P Montemurro1, M Coluccia, L De Nicolò
1Istituto di Patologia Generale, Università di Bari, Italy.
Abstract:
Using a mouse model, we have investigated the in vivo effect of cyclosporin on macrophage procoagulant activity and on plasma levels of plasminogen activator inhibitor. Procoagulant activity of peritoneal macrophages was studied after treatment of mice with different regimens of cyclosporin (10 to 100 mg/kg body weight) for seven days. No significant difference was found between treated and control animals in both basal procoagulant activity and procoagulant activity generated during short-term culture in the absence or in the presence of endotoxin. These findings are in striking contrast with in vitro experiments showing that cyclosporin induced a significant increase in procoagulant activity when added to peritoneal macrophages from normal animals before challenge with endotoxin (p less than 0.01). Plasma levels of plasminogen activator inhibitor in cyclosporin-treated mice were not different from those of controls. It is suggested that factors other than monocyte-macrophage procoagulant activity or plasminogen activator inhibitor may be important for the postulated 'prothrombotic' action of cyclosporin.
Insights
Cyclosporin did not alter macrophage procoagulant activity or plasminogen activator inhibitor levels in vivo. This contrasts with in vitro findings, suggesting other mechanisms for cyclosporin's prothrombotic effects.
Area of Science:
- Immunology
- Pharmacology
- Hematology
Background:
- Cyclosporin is an immunosuppressant drug.
- Its potential prothrombotic effects are debated.
- Macrophage procoagulant activity and plasminogen activator inhibitor are key hemostatic factors.
Purpose of the Study:
- To investigate the in vivo effects of cyclosporin on macrophage procoagulant activity.
- To assess plasma levels of plasminogen activator inhibitor in cyclosporin-treated mice.
Main Methods:
- A mouse model was used to study cyclosporin's effects.
- Mice received varying cyclosporin doses (10-100 mg/kg) for seven days.
- Peritoneal macrophage procoagulant activity and plasma plasminogen activator inhibitor levels were measured.
Main Results:
- No significant difference in macrophage procoagulant activity was observed between cyclosporin-treated and control mice, in vitro or in vivo.
- Cyclosporin significantly increased macrophage procoagulant activity in vitro (p < 0.01).
- Plasma plasminogen activator inhibitor levels remained unchanged in treated mice.
Conclusions:
- In vivo cyclosporin administration does not affect macrophage procoagulant activity or plasminogen activator inhibitor levels.
- The prothrombotic effects of cyclosporin may involve mechanisms independent of these factors.
- Further research is needed to elucidate cyclosporin's in vivo prothrombotic mechanisms.