PMID- 9843893
OWN - NLM
STAT- MEDLINE
DCOM- 19990201
LR  - 20190219
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 275
IP  - 6
DP  - 1998 Dec
TI  - IL-6 is essential in TNF-alpha-induced fever.
PG  - R2028-34
LID - 10.1152/ajpregu.1998.275.6.R2028 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine that 
      orchestrates an array of local and systemic effects. For instance, acute exposure 
      to a high dose of TNF-alpha results in septic shock and fever. We have used 
      interleukin-1beta (IL-1beta)- and interleukin-6 (IL-6)-deficient mice, along with 
      their wild-type equivalents, to define a role for TNF-alpha in fever. Briefly, 
      the mice produced prostaglandin E2-dependent fevers in response to recombinant 
      murine TNF-alpha (rmTNF-alpha). Furthermore, rmTNF-alpha (12 microgram/mouse ip) 
      triggered a febrile response in IL-1beta-deficient mice as well as in their 
      corresponding wild-type controls. In contrast, the IL-6-deficient mice were 
      resistant to rmTNF-alpha (4.5 microgram/mouse ip), although their wild-type 
      counterparts readily mounted a fever. In the IL-6-deficient mice, moreover, the 
      febrile response to rmTNF-alpha could be restored by a central administration of 
      rat recombinant IL-6 (500 ng/mouse icv). We thus conclude that TNF-alpha can 
      trigger fever independent of IL-1beta but dependent on IL-6. We also suggest that 
      central, rather than peripheral, IL-6 (plasma IL-6 was measured 2 h after 
      pyrogenic challenge) is essential in TNF-alpha-induced fever.
FAU - Sundgren-Andersson, A K
AU  - Sundgren-Andersson AK
AD  - Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories for 
      Natural Sciences, Stockholm University, S-10691 Stockholm, Sweden.
FAU - Ostlund, P
AU  - Ostlund P
FAU - Bartfai, T
AU  - Bartfai T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Fever/*chemically induced/*physiopathology
MH  - Humans
MH  - Injections, Intraperitoneal
MH  - Injections, Intraventricular
MH  - Interleukin-1/deficiency/genetics
MH  - Interleukin-6/deficiency/genetics/pharmacology/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout/genetics
MH  - Rats
MH  - Recombinant Proteins
MH  - Reference Values
MH  - *Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1998/12/09 00:00
MHDA- 1998/12/09 00:01
CRDT- 1998/12/09 00:00
PHST- 1998/12/09 00:00 [pubmed]
PHST- 1998/12/09 00:01 [medline]
PHST- 1998/12/09 00:00 [entrez]
AID - 10.1152/ajpregu.1998.275.6.R2028 [doi]
PST - ppublish
SO  - Am J Physiol. 1998 Dec;275(6):R2028-34. doi: 10.1152/ajpregu.1998.275.6.R2028.