IL-1 type I receptor mediates acute phase response to turpentine, but not lipopolysaccharide, in mice

1996 ◽  
Vol 271 (6) ◽  
pp. R1668-R1675 ◽  
Author(s):  
L. R. Leon ◽  
C. A. Conn ◽  
M. Glaccum ◽  
M. J. Kluger

This study examined the role of the interleukin-1 (IL-1) type I receptor (IL-1RtI) in the acute phase response (APR) to inflammation in mice. Turpentine (100 microliters/mouse) injected subcutaneously induced fever, lethargy, body weight loss, and anorexia in IL-1RtI wild-type mice. Knockout mice lacking the IL-1RtI were resistant to these effects of turpentine, supporting a role for this receptor in the APR to local inflammation. The intraperitoneal injection of a low (50 micrograms/kg) or high (2.5 mg/kg) dose of lipopolysaccharide (LPS) induced similar APRs in IL-1RtI wild-type and knockout mice. IL-1RtI knockout mice were resistant to the APR induced by peripherally injected murine IL-1 beta, suggesting that it is not the interaction of endogenous IL-1 beta with IL-1RtII that induces an APR to LPS in these mice. We speculate that the absence of IL-1RtI in these knockout mice results in the sensitization of other cytokine pathways to mediate the APR to LPS.

2000 ◽  
Vol 278 (4) ◽  
pp. R824-R830 ◽  
Author(s):  
Michael D. Josephs ◽  
Carmen C. Solorzano ◽  
Michael Taylor ◽  
Jason J. Rosenberg ◽  
Daniel Topping ◽  
...  

A complete understanding of the role for endogenously produced interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and IL-1 receptor antagonist (IL-1ra) in the acute phase response to inflammation remains unknown. In the present studies, knockout mice lacking either a functional IL-1 type I receptor (IL-1RI− / −), a TNF type I receptor (TNFR-I− / −), or both IL-1 type I and TNF type I receptors (IL-1RI− / −/TNFR-I− / −) received a turpentine abscess. Additional mice deficient in IL-1ra protein (IL-1ra− / −) or overexpressing IL-1ra protein (IL-1ratg) were similarly treated. After a turpentine abscess, IL-1 receptor knockout mice exhibited an attenuated inflammatory response compared with wild-type or animals lacking a functional TNFR-I. Mice overexpressing IL-1ra also had an attenuated hepatic acute phase protein response, whereas IL-1ra knockout mice had a significantly greater hepatic acute phase response. We conclude that the inflammatory response to a turpentine abscess is the result of a balance between IL-1ra expression and IL-1 binding to its type I receptor. Endogenously produced IL-1ra plays a central role in mitigating the magnitude of the IL-1-mediated inflammatory response and, ultimately, the outcome to a turpentine abscess.


1998 ◽  
Vol 18 (12) ◽  
pp. 7269-7277 ◽  
Author(s):  
Bonnie L. Burgess-Beusse ◽  
Gretchen J. Darlington

ABSTRACT Members of the C/EBP (CCAAT/enhancer binding protein) family of transcription factors play important roles in mediating the acute-phase response (APR), an inflammatory process resulting from infection and/or tissue damage. Among the C/EBP family of proteins, C/EBPβ and -δ were thought to be the primary mediators of the APR. The function of C/EBPα in the APR has not been fully characterized to date. Here, we investigate the role of C/EBPα in the APR by using neonatal mice that lack C/EBPα expression. Northern blot analysis of acute-phase protein gene expression in neonatal mice treated with purified bacterial lipopolysaccharide or recombinant interleukin 1β as an inflammation stimulus showed a strong APR in wild-type mice, but a response in C/EBPα null animals was completely lacking. The C/EBPα knockout and wild-type mice demonstrated elevations in C/EBPβ and -δ mRNA expression and DNA binding as well as increased DNA binding of NF-κB, all of which are known to be important in the APR. Null mice, however, failed to activate STAT3 binding in response to lipopolysaccharide. Our results provide the first evidence that C/EBPα is absolutely required for the APR in neonatal mice, is involved in STAT3 regulation, and cannot be compensated for by other C/EBP family members.


1987 ◽  
Vol 252 (1) ◽  
pp. E27-E32 ◽  
Author(s):  
S. E. Goldblum ◽  
D. A. Cohen ◽  
M. Jay ◽  
C. J. McClain

The mechanism(s) of stress-induced hypoferremia and hypozincemia remains unclear. We studied the role of granulocytes and lactoferrin (LF) in endotoxin and murine interleukin 1 (IL-1)-induced depression of serum Fe and Zn concentrations in both rabbits and rats. Both endotoxin and IL-1 administration induced significant hypoferremia (P less than 0.01) and hypozincemia (P less than 0.01) after 6 h in both species. Granulocyte depletion before IL-1 infusion significantly (P less than 0.01) diminished the hypoferremia but not the hypozincemia. Moreover, infusion of 5 or 15 mg of human LF into rabbits caused significant hypoferremia (P less than 0.005) without hypozincemia. Significant hypozincemia (P less than 0.01) could only be demonstrated after a 75-mg infusion. In contrast, infusions of human transferrin at equivalent doses (5, 15, and 75 mg) induced neither hypoferremia nor hypozincemia. Therefore endotoxin and IL-1-induced hypoferremia and, to a much lesser degree, hypozincemia are granulocyte dependent. Granulocyte released LF is a specific carrier molecule for transport and removal of Fe from the circulation during the acute phase response. The data suggest a mechanistic dissociation of IL-1-induced hypoferremia and hypozincemia with LF-independent mechanisms for Zn.


Cytokine ◽  
1995 ◽  
Vol 7 (6) ◽  
pp. 510-516 ◽  
Author(s):  
Hester S.A. Oldenburg ◽  
Hester S.A. Oldenburg ◽  
Jeffrey H. Pruitt ◽  
Douglas D. Lazarus ◽  
Douglas D. Lazarus ◽  
...  

Author(s):  
Devin I. Alewel ◽  
Andres R. Henriquez ◽  
Catherine H. Colonna ◽  
Samantha J. Snow ◽  
Mette C. Schladweiler ◽  
...  

1991 ◽  
Vol 12 (2) ◽  
pp. 268 ◽  
Author(s):  
H. Rieder ◽  
G. Ramadori ◽  
K.-H.Meyer zum Büschenfelde

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