The Role of Inflammatory Mediators in the Mechanism of the Host Immune Response Induced by Ischemia-Reperfusion Injury

Immunol Invest. 2000 Feb;29(1):13-26. doi: 10.3109/08820130009105141.

Abstract

Our previous study suggested that inflammatory mediators released due to IRI lead to host's immune response by upregulating MHC II in the host's peripheral T lymphocytes. This study hypothesized the role of platelet-activating factor (PAF) in the mechanism of induced MHC II upregulation due to IRI on peripheral T lymphocytes. The objectives of this study were to investigate the role of PAF in the induction of host immune reactivity and the protective effect of PAF-antagonist TCV-309 in combination with prostaglandin E1 (PGE1) against the host's immune response caused by IRI. Thirty female domestic swine were divided into three groups. Group A (6 donors, 6 recipients) had no pharmacological intervention. Group B (6 donors, 6 recipients) was the experimental group treated with TCV-309 + PGE1. Group C underwent sham operation. The ex vivo preservation time for groups A and B was 4 hr at 4 degrees C. To detect the changes in MHC II expression on T cells due to IRI, blood samples were collected before reperfusion (baseline level), 1, 2, and 3 days post-reperfusion. Two-colour flow cytometry analysis (FACS) was used to study MHC II-DR-beta expression in peripheral T lymphocytes. Swine anti-MHC II and anti-CD3 antibodies were used for this purpose. The FACS analyses demonstrated that in group A, there was a significant increase (p < 0.05) in MHC II intensity on peripheral T lymphocytes on day 2 post-reperfusion. By the third day post-reperfusion, MHC intensity had a tendency to decrease but did not reached the baseline level. In group B and C, however, there was no significant change in the level of MHC II in T lymphocytes at any of the post-reperfusion times. In group A, the number of CD3+MHC+ T lymphocytes significantly decreased (p < 0.05) by one day post-reperfusion and remained at this level until the third day post-reperfusion. In groups B and C, no significant change in the number of CD3+MHC+ T cells was observed. The results of this study suggested that the release of inflammatory mediators (e.g. PAF) due to IRI played a role in the mechanism of IRI-induced host's immune response. The results also suggested that the combination of TCV-309 + PGE1 could reduce this immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alprostadil / administration & dosage
  • Animals
  • Female
  • Histocompatibility Antigens Class II / biosynthesis
  • Inflammation Mediators / physiology*
  • Infusions, Intravenous
  • Isoquinolines / pharmacology
  • Isoquinolines / therapeutic use
  • Platelet Activating Factor / physiology
  • Pyridinium Compounds / pharmacology
  • Pyridinium Compounds / therapeutic use
  • Regression Analysis
  • Reperfusion Injury / immunology*
  • Reperfusion Injury / metabolism
  • Swine
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / metabolism
  • Tetrahydroisoquinolines*
  • Up-Regulation / immunology

Substances

  • Histocompatibility Antigens Class II
  • Inflammation Mediators
  • Isoquinolines
  • Platelet Activating Factor
  • Pyridinium Compounds
  • Tetrahydroisoquinolines
  • Alprostadil
  • TCV 309