Endotoxin & Cytokines. Do Protein Loss and Metabolic Effects Depend on Central Nervous System (CNS) Activation of Stress Hormones or on Local Mechanisms in Muscle and Fat?

Summary

Main objective : The purpose of this study is to prove that the effects of bacterial endotoxin and cytokine TNF-α, on protein loss, fatty acid release, and glucose metabolism depend on two mechanisms: 1. Direct local effects in muscle tissue. 2. Activation of the hypothalamo-pituitary axis and a stress-hormone response Study protocols: 1. Acute metabolic effects of TNF-α(Beromun, Boehringer-Ingelheim Germany) vs placebo perfused into the femoral artery of the leg in 8 healthy subjects. 2. Acute metabolic effects of * placebo(saline) * endotoxin(US standard reference E.Coli, endotoxin) * TNF-α(Beromun, Boehringer-Ingelheim Germany) given systemically * in 8 patients with hypopituitarism(to block stress hormone release) and in 8 healthy subjects all studied thrice.

Timeline

Start

2010-06

Primary completion

2013-01

Completion

2013-01

Publications

• Bach E, Nielsen RR, Vendelbo MH, Moller AB, Jessen N, Buhl M, K-Hafstrom T, Holm L, Pedersen SB, Pilegaard H, Bienso RS, Jorgensen JO, Moller N. Direct effects of TNF-alpha on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release. Diabetes. 2013 Dec;62(12):4023-9. doi: 10.2337/db13-0138. Epub 2013 Jul 8.

Drugs

Indications