Nicotinamide inhibits endotoxin-induced monocyte tissue factor expression.
BACKGROUND
Tissue factor (TF) is the main initiator of blood coagulation in vivo. Its increased expression on activated monocytes is associated with thrombotic complications and mortality in conditions such as sepsis, disseminated intravascular coagulation and coronary artery disease.


OBJECTIVE
The effect of the vitamin B derivative nicotinamide on endotoxin-induced monocyte TF and CD11b expression, soluble interleukin(IL)-6, and clotting onset time (COT) was studied.


METHODS
Experiments were conducted in human peripheral blood leukocyte suspensions and in whole blood from eight healthy volunteers. Free oscillating rheometry (measuring COT) and flow cytometry were applied to evaluate the effect of endotoxin on TF, CD11b, IL-6 and the overall coagulation response of plasma supplemented with activated autologous leukocytes.


RESULTS
In response to endotoxin, there was an increase in IL-6, TF and CD11b expression and a procoagulant shift of COT. At 4 mmol L-1 nicotinamide, inhibition of TF expression and IL-6 and a normalization of COT were seen. At 16 mmol L-1 nicotinamide, CD11b decreased also. The level of monocyte TF expression correlated with the COT readings, and the endotoxin-induced procoagulant shift of COT could be totally inhibited by blocking TF with an inhibitory antibody.


CONCLUSIONS
These results demonstrate the ability of nicotinamide to inhibit the activation of coagulation associated with endotoxemia. We have previously shown that nicotinamide exerts strong anti-inflammatory effects. Evidence is accumulating for nicotinamide to have a therapeutic potential in modulating disease states in which there is a profound activation of coagulation and inflammation, such as in sepsis and disseminated intravascular coagulation.
Ungerstedt
J S
JS
Coagulation Research, Department of Surgical Sciences,Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden. johanna.ungerstedt@ks.se
Heimersson
K
K
Söderström
T
T
Hansson
M
M
D000328:Adult; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D039481:CD11b Antigen / Q000097:blood; D004336:Drug Antagonism; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000737:chemistry; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology*; D013925:Thromboplastin / Q000096:biosynthesis / Q000187:drug effects*
D039481:CD11b Antigen; D004731:Endotoxins; D015850:Interleukin-6; D009536:Niacinamide; D013925:Thromboplastin