| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Canada
2 Department of Endocrinology, National Institute for Biological Standards and Control, Potters Bar, United Kingdom
* To whom correspondence should be addressed. E-mail: giamal.luheshi{at}mcgill.ca.
Interleukin (IL)-6 is an important humoral mediator of fever following infection and inflammation and satisfies a number of criteria for a circulating pyrogen. However, evidence supporting such a role is diminished by the moderate or even absent ability of the recombinant protein to induce fever and activate the cyclooxygenase (COX) pathway in the brain, a prerequisite step in the initiation and maintenance of fever. In the present study, we investigated the role of endogenous circulating IL-6 in a rodent model of localized inflammation, by neutralizing its action using a specific antiserum (IL-6AS). Rats were injected with LPS (100 µg kg-1) or saline into a preformed air pouch in combination with an intraperitoneal injection of either normal sheep serum or IL-6AS (1.8 ml rat-1). LPS induced a febrile response, which was accompanied by a significant rise in plasma IL-6 and nuclear STAT3 translocation in endothelial cells throughout the brain 2 h after treatment including areas surrounding the sensory circumventricular organs (sCVO's) and the median preoptic area (MnPO), important regions in mediating fever. These responses were abolished in the presence of the IL-6AS, which also significantly inhibited the LPS-induced upregulation of mRNA expression or immunoreactivity (IR) of the inducible form of cyclooxygenase, the rate limiting enzyme for prostaglandin (PG)E2-synthesis. Interestingly, nuclear STAT3 positive cells, co-localized with COX2-IR, signifying that IL-6-activated cells are directly involved in PGE2 production. These observations suggest that IL-6 is an important circulating pyrogen that activates the COX2-pathway in cerebral microvasculature, most likely through a STAT3 dependent pathway.
This article has been cited by other articles:
|
|
 |
|
  W. Inoue, G. Somay, S. Poole, and G. N. Luheshi Immune-to-brain signaling and central prostaglandin E2 synthesis in fasted rats with altered lipopolysaccharide-induced fever Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R133 - R143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Matsumura, T. Shibakusa, T. Fujikawa, H. Yamada, K. Matsumura, K. Inoue, and T. Fushiki Intracisternal administration of transforming growth factor- evokes fever through the induction of cyclooxygenase-2 in brain endothelial cells Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R266 - R275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aguilar-Valles, S. Poole, Y. Mistry, S. Williams, and G. N. Luheshi Attenuated fever in rats during late pregnancy is linked to suppressed interleukin-6 production after localized inflammation with turpentine J. Physiol., August 15, 2007; 583(1): 391 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Greis, J. Murgott, S. Rafalzik, R. Gerstberger, T. Hubschle, and J. Roth Characterization of the febrile response induced by fibroblast-stimulating lipopeptide-1 in guinea pigs Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R152 - R161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ashdown, S. Poole, P. Boksa, and G. N. Luheshi Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1667 - R1674. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
