Inflammatory Cytokine Production in Whole Blood Modified by Liposome-Encapsulated Hemoglobin

Abstract

The effect of Neo Red Cells (NRC), liposome-encapsulated hemoglobin, on production of tumor necrosis factor alpha (TNF-a) and interleukin-6 (IL-6) were studied in whole blood preparations ex vivo. Venous blood was collected with heparin and incubated in a CO2 incubator. Treatment of blood samples with NRC reduced the constitutive levels of TNF-a and IL-6. Lipopolysaccharide (LPS) treatment for 24 h increased production of TNF-a and IL-6 in a dose-dependent manner. Pretreatment with NRC (5%) for 24 h markedly potentiated the LPS-induced TNF-a production and, that of IL-6 to a lesser extent. Northern bloting analysis of total RNA in whole blood showed that pretreatment with NRC caused a marked increase in TNF-a mRNA expression in response to LPS. It is concluded that NRC potentiates LPS-induced TNF-a and IL-6 production in whole blood ex vivo, and that the potentiating effect of NRC on LPS-induced TNF-a production can be attributed, at least in part, to an increase in its mRNA expression.