Pentoxifylline attenuates stored blood-induced inflammation: A new perspective on an old problem.
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.
Deree
Jessica
J
Division of Trauma and Surgical Critical Care, Department of Surgery, University of California San Diego School of Medicine, San Diego, CA, USA.
Lall
Rohan
R
Melbostad
Heidi
H
Loomis
William
W
Hoyt
David B
DB
Coimbra
Raul
R
D015703:Antigens, CD / Q000378:metabolism; D001793:Blood Preservation / Q000379:methods*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018929:Cell Culture Techniques; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D058851:GPI-Linked Proteins; D006401:Hematologic Agents / Q000494:pharmacology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015703:Antigens, CD; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D006401:Hematologic Agents; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; D010431:Pentoxifylline