Pentoxifylline attenuates stored blood-induced inflammation: A new perspective on an old problem

Surgery. 2006 Aug;140(2):186-91. doi: 10.1016/j.surg.2006.03.013.

Abstract

Background: Blood transfusion is a risk factor for many inflammatory processes. Its supernatant fraction has been proven to activate neutrophils. We hypothesized that pentoxifylline (PTX) would attenuate stored blood-induced neutrophil activation and pro-inflammatory mediator production.

Methods: Whole blood was incubated with HBSS, LPS (100 microg/mL), leukoreduced PRBC supernatant + LPS, or supernatant + LPS + PTX (2 mmol/L). TNF-alpha levels were measured by ELISA. MMP-9 was evaluated with zymography. Neutrophil CD66b expression was determined by flow cytometry in blood treated with HBSS, fMLP (1 micromol/L), supernatant + fMLP, or supernatant + fMLP + PTX.

Results: TNF-alpha levels were elevated in both the LPS and supernatant + LPS groups (100%; P < 0.01 and 120%; P < 0.01, respectively). PTX administration resulted in a 106% decrease in TNF-alpha (P < 0.0001). MMP-9 levels were increased in all groups. Administration of PTX to the supernatant + LPS group generated a 33% decrease in MMP-9 levels, which was not statistically significant (P < 0.4). Upregulation of CD66b expression was seen in LPS and supernatant + LPS groups. Significant attenuation was seen with PTX (47%; P < 0.01).

Conclusions: PTX downregulates CD66b and TNF-alpha expression in supernatant-induced whole blood. Because blood transfusion can contribute to inflammatory injury, the adjunctive use of PTX may have therapeutic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Blood Preservation / methods*
  • Cell Adhesion Molecules / metabolism
  • Cell Culture Techniques
  • Erythrocytes / drug effects*
  • Erythrocytes / metabolism
  • GPI-Linked Proteins
  • Hematologic Agents / pharmacology*
  • Humans
  • Matrix Metalloproteinase 9 / metabolism*
  • Neutrophils / physiology
  • Pentoxifylline / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Antigens, CD
  • CEACAM8 protein, human
  • Cell Adhesion Molecules
  • GPI-Linked Proteins
  • Hematologic Agents
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 9
  • Pentoxifylline