Biomedical subjects

I Hardardóttir

Publications and source records attributed to I Hardardóttir.

11 recordsLinked to original sources

PubMed1998

Beneficial effects of cytokine induced hyperlipidemia.

Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and lipoproteins binding toxic agents and neutralizing their harmful effects. Thus, cytokines induce marked changes in lipid metabolism that lead to hyperlipidemia which represents part of the innate immune response and may be beneficial to the host.

Acute-Phase Proteins↗

PubMed1997

LPS and cytokines regulate extra hepatic mRNA levels of apolipoproteins during the acute phase response in Syrian hamsters.

Altered hepatic expression of apolipoproteins occurs during the acute phase response. Here we examined whether the acute phase response alters extra hepatic expression of apolipoproteins. Syrian hamsters were injected with endotoxin (LPS), tumor necrosis factor (TNF), interleukin (IL)-1, or the combination of TNF + IL-1 and mRNAs for serum amyloid A (apoSAA), apolipoprotein (apo) J, apo E. apo A-I, and apo D, were analyzed. LPS increased mRNA levels for apoSAA in all tissues examined. LPS and TNF + IL-1 increased mRNA levels for apo J in kidney, heart, stomach, intestine, and muscle. Individually, TNF and IL-1 were less potent than the combination of the two cytokines. LPS decreased mRNA levels for apo E in all tissues, except for mid and distal intestine. TNF and IL-1 were less effective than LPS. LPS, TNF + IL-1 and TNF decreased mRNA levels for apo A-I in duodenum. mRNA for apo D decreased in heart, were unchanged in brain and increased in muscle, following LPS. The widespread extra hepatic regulation of the apolipoproteins during the acute phase response may be important for the alterations in lipid metabolism that occur during infection and inflammation as well as the immune response.

Acute-Phase Reaction↗

PubMed1997

Dietary fish oil supplementation increases survival in mice following Klebsiella pneumoniae infection.

The effect of dietary fish-oil supplementation on survival of NMRI mice after Klebsiella pneumoniae infection was investigated. 30 mice in each group were fed a fish-oil enriched diet, olive-oil enriched diet or standard chow diet. After 6 weeks, the mice were injected intramuscularly with Klebsiella pneumoniae. After 120 h the survival of the mice fed fish-oil enriched diet was 40%, while the survival for mice fed standard or olive-oil enriched diets was 20% and 25%, respectively. The survival curve over 120 h was significantly improved (p = 0.0034) for mice fed a fish-oil enriched diet, compared to the survival curves for mice fed the other 2 diets. The study was repeated by comparing the survival of mice fed a fish-oil enriched diet to those given a corn-oil enriched diet. After 120 h the survival curve for mice fed the fish-oil enriched diet was significantly better compared to the survival curve for mice given the corn-oil enriched diet (p = 0.01). A fish-oil enriched diet therefore increases survival in mice following Klebsiella pneumoniae infection, whether compared to a standard diet, olive-oil enriched diet or corn-oil enriched diet.

Animals↗

PubMed1996

Endotoxin and cytokines decrease serum levels and extra hepatic protein and mRNA levels of cholesteryl ester transfer protein in syrian hamsters.

Endotoxin alters the metabolism of lipoproteins, including that of high density lipoprotein (HDL). Cholesteryl ester transfer protein (CETP) facilitates exchange of HDL cholesterol for very low density lipoprotein (VLDL) triglyceride, leading to catabolism of HDL. We investigated the effects of endotoxin and cytokines on CETP in Syrian hamsters. Endotoxin induced a rapid and progressive decrease in serum CETP levels, by 48 h CETP had decreased to < 20% of control levels. Endotoxin also decreased CETP mRNA and protein levels in adipose tissue, heart, and muscle, the tissues with highest levels of CETP mRNA, providing a plausible mechanism for the endotoxin-induced decrease in circulating CETP. Dexamethasone did not mimic the effects of endotoxin on CETP, but the combination of tumor necrosis factor and interleukin-1 did, indicating that these cytokines may in part mediate the effects of endotoxin on CETP. The endotoxin-induced decrease in CETP may help maintain HDL cholesterol levels during infection and inflammation when increased triglyceride levels could drive the exchange of HDL cholesteryl ester for VLDL triglyceride. Maintaining circulating HDL may be important because HDL protects against the toxic effects of endotoxin and provides cholesterol for peripheral cells involved in the immune response and tissue repair.

Adipose Tissue↗

PubMed1995

Effects of endotoxin on lipid metabolism.

Endotoxin, via cytokines, induces marked changes in lipid metabolism which are now considered part of the acute phase response. The endotoxin induced hyperlipidemia may represent a nonspecific immune response that can decrease the toxicity of a variety of harmful biological and chemical agents and serve to redistribute nutrients to cells important in host defense. The endotoxin induced changes in lipid metabolism may therefore be beneficial.

Animals↗

PubMed1994

Effects of endotoxin and cytokines on lipid metabolism.

Endotoxin, via cytokines, induces marked changes in lipid metabolism: serum VLDL increases, whereas the effect on LDL levels varies among species. The increase in VLDL is caused by stimulation of hepatic VLDL secretion or inhibition of clearance, or both. These alterations can be deleterious or beneficial effects.

Animals↗

PubMed1994

Endotoxin and cytokines increase hepatic messenger RNA levels and serum concentrations of apolipoprotein J (clusterin) in Syrian hamsters.

Infection and inflammation induce alterations in hepatic synthesis and plasma concentrations of the acute phase proteins. Our results show that apolipoprotein (apo) J is a positive acute phase protein. Endotoxin (LPS), tumor necrosis factor (TNF), and interleukin (IL)-1 increased hepatic mRNA and serum protein levels of apo J in Syrian hamsters. Hepatic apo J mRNA levels increased 10- to 15-fold with doses of LPS from 0.1 to 100 micrograms/100 g body weight within 4 h and were elevated for > or = 24 h. Serum apo J concentrations were significantly increased by 16 h and further elevated to 3.3 times that of control, 24 h after LPS administration. Serum apo J was associated with high density lipoprotein and increased fivefold in this fraction, after LPS administration. Hepatic apo J mRNA levels increased 3.5- and 4.6-fold, with TNF and IL-1, respectively, and 8.2-fold with a combination of TNF and IL-1. Serum apo J concentrations were increased 2.3-fold by TNF, 79% by IL-1, and 2.9-fold with a combination of TNF and IL-1. These results demonstrate that apo J is a positive acute phase protein.

Amino Acid Sequence↗

PubMed1994

Effects of TNF, IL-1, and the combination of both cytokines on cholesterol metabolism in Syrian hamsters.

Infection and inflammation are associated with alterations in lipid metabolism that may be mediated by cytokines such as TNF and IL-1. This study determined the effects of TNF and IL-1 on certain aspects of cholesterol metabolism. TNF or IL-1 administration to Syrian hamsters increased serum cholesterol levels by 17 and 21%, respectively, and decreased HDL cholesterol levels by 20 and 15%, respectively. TNF + IL-1 increased serum cholesterol levels by 58% and decreased HDL cholesterol levels by 58%. TNF or IL-1 increased hepatic HMG CoA reductase mRNA levels by 3.5- and 3-fold, respectively. TNF + IL-1 increased HMG CoA reductase mRNA levels by 7-fold. IL-1 increased hepatic LDL receptor mRNA levels by 2-fold while TNF and a combination of TNF + IL-1 had minimal effects. TNF or IL-1 did not affect hepatic apo E or apo A-I mRNA levels while a combination of TNF + IL-1 decreased both mRNA levels by 50%. Our results demonstrate that TNF and IL-1 similarly affect the parameters of cholesterol metabolism studied. Furthermore, the combination of TNF + IL-1 was, in most cases, more effective than either cytokine alone, and reproduced many of the effects of LPS.

Animals↗

PubMed1993

Dietary arachidonate enhances tissue arachidonate levels and eicosanoid production in Syrian hamsters.

Eicosanoids are oxidative derivatives of arachidonic acid. When produced in excess many of them are proinflammatory agents. This study investigates whether dietary arachidonic acid enhances arachidonic acid phospholipid content of various tissues and whether this enrichment increases eicosanoid production. Male Syrian hamsters were divided into four groups and fed diets supplemented with ethyl esters of oleic acid, linoleic acid, arachidonic acid or eicosapentaenoic acid. Differences in the composition of the phospholipid fatty acids were monitored in liver, lung, heart, spleen, kidney, testes, macrophages and platelets. In all tissues analyzed, the phospholipid content of arachidonic acid was significantly higher in the arachidonic dietary group compared with all other dietary groups (average > 50% higher). In contrast, increasing dietary linoleic acid by 50% had little effect on altering tissue arachidonic acid levels. Following in vitro stimulation, macrophages and platelets from animals maintained on arachidonic acid produced, in general, the highest levels of eicosanoids compared with cells from animals fed the other diets. Significant differences were observed in prostaglandin E2 (macrophages) and thromboxane B2 (platelets) formation when compared with the oleic acid and eicosapentaenoic acid dietary groups. The data demonstrate that including low to moderate levels of arachidonic acid in the diet increases macrophage and platelet arachidonic acid levels and may augment eicosanoid production.

Analysis of Variance↗

PubMed1992

Cytokines stimulate lipolysis and decrease lipoprotein lipase activity in cultured fat cells by a prostaglandin independent mechanism.

We previously showed that indomethacin blocked the effect of tumor necrosis factor (TNF) and other cytokines on lipolysis. We now show that TNF stimulates prostaglandin (PG) production, enhances lipolysis and decreases lipoprotein lipase (LPL) activity in 3T3-F442A adipocytes and indomethacin blocks these activities, suggesting that the actions of TNF are mediated by PG's. However, exogenous PGE2 at the levels induced by TNF is not sufficient to affect lipolysis or LPL activity and low doses of indomethacin and flurbiprofen block PG production without affecting TNF's action. Interleukin-1 and interferon-alpha and gamma induce lipolysis and decrease LPL activity but do not stimulate much PG production. These results demonstrate that cytokines enhance lipolysis and decrease LPL activity in 3T3 adipocytes by a PG independent mechanism.

3T3 Cells↗

PubMed1992

Increasing the dietary (n-3) to (n-6) polyunsaturated fatty acid ratio increases tumor necrosis factor production by murine resident peritoneal macrophages without an effect on elicited peritoneal macrophages.

Tumor necrosis factor (TNF), prostaglandin (PG) E2 and 6-keto-PGF1 alpha production by murine peritoneal macrophages was monitored following in vitro stimulation with lipopolysaccharide. Macrophages were obtained from mice fed diets containing increasing ratios of (n-3) to (n-6) fatty acids by addition of (n-3) polyunsaturated fatty acids (PUFA) to the (n-6) fatty acids in the diet, or by substituting (n-3) PUFA for the (n-6) fatty acids in the diet. Increasing the dietary (n-3) to (n-6) fatty acid ratio from 0 to 1 increased both cell-associated and secreted TNF production by resident peritoneal macrophages but did not affect TNF production by macrophages elicited with Complete Freund's Adjuvant (CFA). With increasing dietary (n-3): (n-6) ratio there was a decrease in the prostaglandin production by resident peritoneal macrophages, which may partly explain the increased TNF production. The CFA-elicited macrophages produced less prostaglandin than the resident macrophages, and the lower prostaglandin production may partly explain the lack of effect of dietary (n-3) PUFA on TNF production by CFA-elicited macrophages. Increasing the TNF production by resident macrophages with dietary (n-3) PUFA may be beneficial in enhancing antitumor actions and antipathogenicity; by not increasing the high TNF production of inflammatory macrophages, (n-3) PUFA may protect against undesirable systemic inflammatory effects of overproduction.

6-Ketoprostaglandin F1 alpha↗