Kinetics of systemic and intrahypothalamic IL-6 and tumor necrosis factor during endotoxin fever in guinea pigs

1993 ◽  
Vol 265 (3) ◽  
pp. R653-R658 ◽  
Author(s):  
J. Roth ◽  
C. A. Conn ◽  
M. J. Kluger ◽  
E. Zeisberger
Keyword(s):  
Body Temperature ◽  
Tumor Necrosis Factor ◽  
Guinea Pigs ◽  
Tumor Necrosis ◽  
Time Course ◽  
Clear Correlation ◽  
Febrile Response ◽  
Fever Response ◽  
Kinetics Of ◽  
Necrosis Factor

The time course of activity of interleukin-6 (IL-6) and tumor necrosis factor (TNF) was measured in blood plasma and hypothalamic push-pull perfusates during the febrile response to intramuscular injection of bacterial endotoxin (Escherichia coli, 20 micrograms/kg) in 24 guinea pigs. Injection of endotoxin caused a dramatic increase of IL-6 activity in plasma. The logarithmic values of plasma IL-6 activities showed a linear correlation to the febrile change in body temperature (r = 0.898) during the whole time course of fever. IL-6 activity in hypothalamic perfusates increased 12-fold in the first hour after pyrogen application and declined slowly despite the further increase in body temperature. Hypothalamic IL-6 activity did not correlate with the febrile increase in body temperature (r = -0.048). TNF activity in plasma, not detectable before pyrogen application, had its peak in the first hour after endotoxin injection and rapidly declined to 15-20% of the peak activity within the next 2 h and to an undetectable value 5 h after injection. In the hypothalamus TNF was not detectable before endotoxin injection, but it could be monitored in most animals after pyrogen application without a clear correlation to the fever response. These results taken together indicate that endotoxin fever represents a physiological situation in which production and release of cytokines in the peripheral immune system and in the hypothalamus are regulated and stimulated in independent patterns.

The Role of Local Induction of Tumor Necrosis Factor by LPS within a Subcutaneous Air Pouch in the Development of a Febrile Response in Guinea Pigs

2000 ◽  
Vol 7 (4) ◽  
pp. 169-176 ◽  
Author(s):  
Joachim Roth ◽  
Birgit Störr ◽  
Dave Martin ◽  
Karlheinz Voigt ◽  
Eugen Zeisberger
Keyword(s):  
Tumor Necrosis Factor ◽  
Guinea Pigs ◽  
Tumor Necrosis ◽  
Febrile Response ◽  
Air Pouch ◽  
Necrosis Factor

Febrile response to tissue inflammation involves both peripheral and brain IL-1 and TNF-alpha in the rat

1997 ◽  
Vol 272 (3) ◽  
pp. R862-R868 ◽  
Author(s):  
G. N. Luheshi ◽  
A. Stefferl ◽  
A. V. Turnbull ◽  
M. J. Dascombe ◽  
S. Brouwer ◽  
...  
Keyword(s):  
Body Temperature ◽  
Tumor Necrosis Factor ◽  
Intramuscular Injection ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Systemic Injection ◽  
Tissue Inflammation ◽  
Necrosis Factor

We investigated the role and interaction between tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6 in the development of fever and their involvement in brain and systemic pathways in response to localized tissue inflammation caused by injection of turpentine (TPS) in the rat. Intramuscular injection of 10 microl TPS caused significant increases in body temperature, of up to 2 degrees C, compared with saline-treated animals. Fevers were maximal 7-8 h after injection and were preceded by significant increases in plasma bioactive IL-6. No changes in circulating bioactive IL-1 or TNF-alpha were detected. Systemic injection of IL-1 receptor antagonist (IL-1ra, 2 mg/kg i.p.) or anti-TNF-alpha antiserum (0.4 ml i.v.) almost completely abolished the febrile responses to TPS over 8 h and markedly inhibited the rise in plasma IL-6 bioactivity measured 6 h after TPS. To test the involvement of brain cytokines, anti-TNF-alpha antiserum and IL-1ra were injected intracerebroventricularly. Injections of anti-TNF-alpha antiserum (3 microl/rat i.c.v.) or IL-1ra (400 microg/kg i.c.v.) significantly (P < 0.01 and P < 0.05, respectively) inhibited fever induced by TPS. These data suggest that both localized peripheral and brain IL-1 and TNF-alpha are involved directly in the pyrogenic response to inflammation. The results indicate that, in the periphery, IL-1 and TNF-alpha cause increased production of IL-6, the most likely candidate as a circulating endogenous pyrogen.

scholarly journals Tumor Necrosis Factor-alpha, TNFR, And STNFR Relationships to Body Temperature

2019 ◽  
Vol 51 (Supplement) ◽  
pp. 95
Author(s):  
Eliott Arroyo ◽  
Brittany N. Followay ◽  
Jeremiah A. Vaughan ◽  
Joseph A. Laudato ◽  
Brandon M. Gibson ◽  
...  
Keyword(s):  
Body Temperature ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals LIGHT, a Member of the Tumor Necrosis Factor Ligand Superfamily, Prevents Tumor Necrosis Factor-α-mediated Human Primary Hepatocyte Apoptosis, but Not Fas-mediated Apoptosis

2002 ◽  
Vol 277 (51) ◽  
pp. 50054-50061 ◽  
Author(s):  
Hideki Matsui ◽  
Yukiko Hikichi ◽  
Isamu Tsuji ◽  
Takao Yamada ◽  
Yasushi Shintani
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Time Course ◽  
Caspase 3 ◽  
Nuclear Factor Κb ◽  
Caspase 8 ◽  
Death Domain ◽  
Human Primary Hepatocytes ◽  
Induced Apoptosis ◽  
Necrosis Factor

LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its receptors have been identified as lymphotoxin-β receptor (LTβR) and the herpesvirus entry mediator (HVEM)/ATAR/TR2, both of which lack the cytoplasmic sequence termed the “death domain.” The present study has demonstrated that LIGHT inhibits TNFα-mediated apoptosis of human primary hepatocytes sensitized by actinomycin D (ActD), but not Fas- or TRAIL-mediated apoptosis. Furthermore, LIGHT does not prevent some cell lines such as HepG2 or HeLa from undergoing ActD/TNFα-induced apoptosis. This protective effect requires LIGHT pretreatment at least 3 h prior to ActD sensitization. LIGHT stimulates nuclear factor-κB (NF-κB)-dependent transcriptional activity in human hepatocytes like TNFα. The time course of NF-κB activation after LIGHT administration is similar to that of the pretreatment required for the anti-apoptotic effect of LIGHT. LIGHT inhibits caspase-3 processing on the apoptotic protease cascade in TNFα-mediated apoptosis but not Fas-mediated apoptosis. In addition, increased caspase-3 and caspase-8 activities in ActD/TNFα-treated cells are effectively blocked by LIGHT pretreatment. However, LIGHT does not change the expression of TNFRp55, TNFRp75, and Fas. These results indicate that LIGHT may act as an anti-apoptotic agent against TNFα-mediated liver injury by blocking the activation of both caspase-3 and caspase-8.

scholarly journals Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1392-1397 ◽  
Author(s):  
AA te Velde ◽  
RJ Huijbens ◽  
K Heije ◽  
JE de Vries ◽  
CG Figdor
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Time Course ◽  
Interleukin 4 ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Factor Alpha ◽  
Necrosis Factor

Monocytes activated by lipopolysaccharide (LPS) and interferon gamma (IFN gamma) rapidly secrete a number of monokines with different functional properties. Interleukin–4 (IL–4), a T-cell derived cytokine, has been shown to reduce the production of monokines with cytostatic activity for tumor cells, chemotactic activity for monocytes, and factors that stimulate thymocyte proliferation. This latter activity is mediated by a number of monokines like IL–1, tumor necrosis factor alpha (TNF alpha), and IL–6. To elucidate which cytokines produced by monocytes are controlled by IL–4, we tested the effect of IL–4 on the secretion of IL–1 alpha, IL–1 beta, TNF alpha, and IL–6 induced by LPS or IFN gamma. IL–4 was found to inhibit the secretion of IL–1 beta and TNF alpha by activated monocytes almost 100%. The secretion of IL–6 was found to be reduced 70% to 85% in the presence of IL–4, whereas there was no effect on the secretion of IL–1 alpha (IL–1 alpha is mainly cell- associated). Time-course experiments demonstrate that IL–4 reduces the secretion of monokines for a prolonged period of time (greater than 40 hours). The reduced secretion of IL–1 beta and TNF alpha was specifically induced by IL–4 because anti-IL–4 antiserum completely restored normal monokine production. These data suggest that IL–4 plays a role in the regulation of immune responses by reducing the production of functionally important monokines.

Sign in / Sign up

Export Citation Format

Share Document