In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system. Among these changes, a hypertriglyceridaemic state is frequently evident, resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL). We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells). When originally purified from RAW 264.7 (mouse macrophage) cells, cachectin was shown to have a pI of 4.7, a subunit size of relative molecular mass (Mr) 17,000 and to form non-covalent multimers. A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes. A new high-yield purification technique has enabled us to determine further details of the structure of mouse cachectin. We now report that a high degree of homology exists between the N-terminal sequence of mouse cachectin and the N-terminal sequence recently determined for human tumour necrosis factor (TNF). Purified cachectin also possesses potent TNF activity in vitro. These findings suggest that the 'cachectin' and 'TNF' activities of murine macrophage conditioned medium are attributable to a single protein, which modulates the metabolic activities of normal as well as neoplastic cells through interaction with specific high-affinity receptors.

Identity of tumour necrosis factor and the macrophage-secreted factor cachectin.

Striking elevations in concentrations of total serum lipids were observed in patients with infection caused by gram-negative bacilli. The elevated levels of total lipid in these patients were due mainly to marked increases in serum concentrations of triglycerides or free fatty acids or both. In contrast, patients with severe infection caused by gram-positive cocci had normal concentrations of total serum lipids. Those with fever but no infection and those with influenza had normal concentrations of total serum lipids and normal levels of the major lipid classes. Patients with infectious or serum hepatitis demonstrated a moderate hyperlipidemia, which resulted from increased concentrations of serum triglycerides and free cholesterol. Lipoprotein electrophoresis demonstrated that the hyperlipidemia in patients with severe infection caused by gram-negative bacilli was related to increased levels of pre-beta-lipoproteins. In patients with hepatitis there were increased levels of pre-beta-lipoproteins...

Serum Lipids in Infection

Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.

A variety of invasive stimuli have been shown to induce hyperlipidemia due to impaired removal of triglyceride from the circulation. The mechanism by which endotoxin induces a deficiency in the activity of the key enzyme of triglyceride metabolism, lipoprotein lipase (LPL), has been studied. In C3H/HeN (endotoxin-sensitive) mice, LPL activity in adipose tissue was markedly suppressed 16 h after endotoxin administration. In contrast, the endotoxin-resistant C3H/HeJ mice were less sensitive to the suppressive effect of endotoxin on LPL activity. After endotoxin administration, a transferable factor had been detected in the blood of C3H/HeN mice 2 h after the injection of endotoxin that causes a suppression of adipose tissue LPL activity in C3H/HeJ mice as well as in C3H/HeN mice. Conditioned medium from the cultures of peritoneal exudate cells of C3H/HeN mice incubated in endotoxin also suppresses adipose tissue LPL in C3H/HeJ mice. These studies demonstrate that exudate cells produce a humoral factor in response to endotoxin, which suppresses adipose tissue LPL.

https://rupress.org/jem/article-pdf/154/3/631/1092169/631.pdf

Studies of endotoxin-induced decrease in lipoprotein lipase activity.

https://www.gastrojournal.org/article/S0016-5085(82)80403-4/pdf

Rosemary I. Travers

Papers

Hyperlipidemia, fatty liver, and bromsulfo-phthalein retention in rabbits injected intravenously with bacterial endotoxins

Movement of lipids into and out of the blood during hyperlipidemia induced in rabbits by pituitary extract and fraction H.