Heparin fails to inhibit the leukocyte recruitment for an extended time following inflammatory stimulus

Pharm Biol. 2015 Jan;53(1):72-7. doi: 10.3109/13880209.2014.910534. Epub 2014 Oct 7.

Abstract

Context: Several studies have shown that heparin is able to inhibit leukocyte recruitment during an early acute inflammatory response. However, considering the pharmacokinetic aspects of heparin and the dynamics of inflammation our objective was to determine if heparin is able to retain its antimigratory property during a prolonged inflammatory response.

Objective: Compare the effect of heparin on leukocyte recruitment to the peritoneal cavity during early acute inflammatory response and for a longer time post-inflammatory stimulus.

Materials and methods: Wistar rats pre-treated with subcutaneous heparin in doses of 1, 5, and 15 µg/kg were challenged with 2 mL intraperitoneal thioglycollate. After 3 or 8 h, the animals were killed. The cells in the peritoneal cavity were collected and counted. For differential counting, cells from peritoneal lavage and from blood were distended over a glass slide, stained, and counted.

Results: After 3 h, heparin inhibited cell influx to the injury site at all tested dosages. The largest effect was achieved at a 5 µg/kg dose (83% of reduction, p < 0.001). After 8 h, heparin at a 1 µg/kg dose reduced 63% of cellular infiltration (p < 0.001); the group treated with a 15 µg/kg dose presented an pro-inflammatory effect observed by the higher proportions, when compared with the thioglycollate group, of neutrophils on whole blood (60.9%, p < 0.001) and peritoneal fluid (27.3%, p < 0.05), and whole blood monocytes (117.8%, p < 0.01).

Conclusion: These findings show that the heparin effect on leukocyte recruitment varies depending on its dosage and the duration of the inflammation.

Keywords: Antimigratory property; peritonitis; thioglycollate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Chemotaxis, Leukocyte / drug effects*
  • Chemotaxis, Leukocyte / immunology
  • Eosinophils / cytology
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Heparin / pharmacology*
  • Leukocyte Count
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Peritoneal Cavity / cytology
  • Peritoneal Lavage
  • Peritonitis / chemically induced
  • Peritonitis / immunology*
  • Rats, Wistar
  • Thioglycolates / pharmacology
  • Time Factors

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Thioglycolates
  • Heparin