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IL-6 is essential in TNF-alpha-induced fever
A K Sundgren-Andersson1, P Ostlund, T Bartfai
1Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories for Natural Sciences, Stockholm University, S-10691 Stockholm, Sweden.
The American Journal of Physiology
|December 9, 1998
Summary
Tumor necrosis factor-alpha (TNF-alpha) induces fever independently of interleukin-1beta (IL-1beta) but requires interleukin-6 (IL-6). Central IL-6 is essential for this TNF-alpha-induced fever response.
Area of Science:
- Immunology
- Neuroscience
- Physiology
Background:
- Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine involved in inflammatory responses, including fever.
- The precise mechanisms by which TNF-alpha induces fever are not fully understood.
- Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are known mediators of fever.
Purpose of the Study:
- To elucidate the specific roles of IL-1beta and IL-6 in TNF-alpha-induced fever.
- To determine whether TNF-alpha-induced fever is dependent on IL-1beta or IL-6.
- To investigate the necessity of central versus peripheral IL-6 in TNF-alpha fever.
Main Methods:
- Utilized IL-1beta-deficient and IL-6-deficient mice, alongside wild-type controls.
- Administered recombinant murine TNF-alpha (rmTNF-alpha) to induce fever.
- Restored fever response in IL-6-deficient mice via central administration of rat recombinant IL-6.
Main Results:
- rmTNF-alpha induced prostaglandin E2-dependent fevers in wild-type and IL-1beta-deficient mice.
- IL-6-deficient mice were resistant to rmTNF-alpha-induced fever.
- Central administration of IL-6 restored the febrile response in IL-6-deficient mice.
Conclusions:
- TNF-alpha triggers fever independently of IL-1beta.
- TNF-alpha-induced fever is critically dependent on IL-6.
- Central IL-6, not peripheral IL-6, is essential for TNF-alpha-induced fever.