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Monocyte B7 and Sialyl Lewis X modulates the efficacy of IL‐10 down‐regulation of LPS‐induced monocyte tissue factor in whole blood
Author(s) -
Warnes Gary,
Biggerstaff John P,
Francis John L
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00788.x
Subject(s) - tissue factor , monocyte , lipopolysaccharide , whole blood , sepsis , in vivo , platelet , cytokine , disseminated intravascular coagulation , coagulation , immunology , pharmacology , chemistry , medicine , biology , microbiology and biotechnology
Recent studies have investigated the use of anti‐inflammatory cytokine, interleukin 10 (IL‐10) to control the development of disseminated intravascular coagulation (DIC) in sepsis by down‐regulation of monocyte tissue factor (MTF) induced by lipopolysaccharide (LPS) in the initial phase of the disease. In vitro and in vivo human studies have shown that a minimal (<1 h) delay in IL‐10 treatment significantly reduces the cytokines ability to inhibit LPS‐induced MTF expression and the end products of coagulation. In this whole blood in vitro study we investigated the role of lymphocyte and platelet interactions with monocytes to up‐regulate MTF expression in the presence of IL‐10 in the initial phase of exposure to LPS. Individual blockade of monocyte B7 or platelet P‐selectin significantly (35%) reduced MTF expression ( P <0.05). IL‐10 showed a dose‐dependent inhibition of LPS (0.1 μg/ml) induced MTF expression, with 56% inhibition at 1 ng/ml, maximizing at 5 ng/ml IL‐10 (75%; P <0.05). Simultaneous exposure to LPS and IL‐10 (1 ng/ml) or addition of IL‐10 1 h after LPS, with individual B7 and P‐selectin blockade significantly enhanced the inhibition of MTF expression by IL‐10 ( P <0.05). We conclude that the efficacy of IL‐10 to control DIC could be enhanced by a simultaneous B7 and P‐selectin blockade.