Subcutaneous and continuous administration of lipopolysaccharide increases serum levels of triglyceride and monocyte chemoattractant protein-1 in rats.
OBJECTIVE
Previous studies have suggested an association between chronic infection and cardiovascular disease, and combined infection/inflammation is frequently related with hypertriglyceridemia, which may be a risk factor of cardiovascular disease. In fact, experimental transient or intermittent administration of lipopolysaccharide (LPS) is known to cause hypertriglyceridemia. We investigated the effects of subcutaneous and continuous administration of LPS in rats, which was considered to mimic chronic infection such as periodontal disease, on the serum levels of lipids [triglyceride (TG), total cholesterol (TC) and free fatty acid (FFA)] and cytokines [tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1)], all of which are thought to be etiological factors of atherosclerotic cardiovascular disease.


METHODS
Ten fasted Wistar rats were subcutaneously injected with LPS (500 micro g/100 g of body weight) (LPS-injected rats; n = 5) or saline (saline-injected rats; n = 5) as a model of transient infection. Further, mini-osmotic pumps containing the same concentration of LPS (LPS-implanted rats; n = 5) or saline (saline-implanted rats; n = 5) were subcutaneously implanted into an additional 10 rats as a model of chronic infection. After the injection or implantation, time-dependent changes in serum levels of TG, TC, FFA, TNF-alpha, MCP-1 and LPS were determined.


RESULTS
LPS was detected in serum until 24 h in LPS-injected rats and until day 5 in LPS-implanted rats. Serum TG levels significantly increased from 6 to 24 h in LPS-injected rats and from day 5 to 14 in LPS-implanted rats. In both LPS-injected and LPS-implanted rats, serum FFA levels increased only slightly, whereas serum TC levels did not appreciably change. Both types of LPS administration increased serum TNF-alpha levels transiently and MCP-1 levels continuously.


CONCLUSIONS
These findings suggest that chronic infection such as periodontal disease induces hypertriglyceridemia and increases serum MCP-1 levels in a manner that increases the risk of atherosclerotic cardiovascular disease.
Department of Periodontology, Showa University Dental School, Tokyo, Japan.
D
D
Uchiumi
M
M
Kobayashi
T
T
Tachikawa
K
K
Hasegawa
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D018932:Chemokine CCL2 / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D022781:Hepatocytes / Q000473:pathology; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018932:Chemokine CCL2; D005230:Fatty Acids, Nonesterified; D008070:Lipopolysaccharides; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D012965:Sodium Chloride; D002784:Cholesterol