Interleukin-10 inhibits lipopolysaccharide-induced upregulation of tissue factor in canine peripheral blood monocytes.

Abstract

The potentially fatal hemostatic disorder of disseminated intravascular coagulation (DIC) is initiated in bacterial sepsis by lipopolysaccharide (LPS)-induced tissue factor (TF) expression on monocytes. Interleukin-10 (IL-10) is a potent inhibitory cytokine that downregulates monocyte inflammatory and procoagulant responses. We hypothesized that canine recombinant IL-10 (rIL-10) would inhibit LPS-induced TF upregulation on canine monocytes in a dose-dependent manner. Canine peripheral blood mononuclear cells (PBMC), obtained by double-density gradient centrifugation, and monocytes, purified from PBMC by immunomagnetic bead separation with an anti-canine CD14 antibody (Ab), were stimulated in suspension with LPS (0.1-1000 ng/mL) for various times. Recombinant IL-10 (10-5000 pg/mL) was added with LPS or up to 2h later. Tissue factor procoagulant activity was measured by cleavage of a chromogenic substrate by activated Factor X generated by the TF-factor VII complex. We found that rIL-10, when given concurrently or 1h after LPS, strongly inhibited LPS-induced TF procoagulant activity in canine PBMC and monocytes. This inhibition was dose-dependent and blocked by an anti-canine IL-10 Ab. Our results indicate that rIL-10 effectively inhibits LPS-induced TF upregulation in canine monocytes and could potentially be useful in limiting the development of DIC in dogs with endotoxemia.

• Authors: Seigo Ogasawara, Tracy Stokol
• Journal: Veterinary immunology and immunopathology (Vet Immunol Immunopathol) Vol. 148 Issue 3-4 Pg. 331-6 (Aug 15 2012) ISSN: 1873-2534 [Electronic] Netherlands
• PMID: 22609246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Lipopolysaccharides
• Interleukin-10
• Thromboplastin

Topics

• Animals
• Blood Coagulation (drug effects, immunology)
• Dogs
• Dose-Response Relationship, Drug
• Female
• Interleukin-10 (pharmacology)
• Leukocytes, Mononuclear (drug effects, immunology)
• Lipopolysaccharides (pharmacology)
• Male
• Monocytes (drug effects, immunology)
• Thromboplastin (antagonists & inhibitors, immunology, physiology)
• Up-Regulation (drug effects, immunology)