TY - JOUR
T1 - Interleukin-6 and tumor necrosis factor in cerebrospinal fluid
T2 - changes during pyrogen fever
AU - Coceani, Flavio
AU - Lees, Jodi
AU - Mancilla, Javier
AU - Belizario, José
AU - Dinarello, Charles A.
N1 - Funding Information:
Acknowledgements. This work was supported by grants from the Medical Research Council of Canada (MT-10518; F.C.) and from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (AI 15614; C.A.D.). The authors thank Dr. Steven Sirko for his contribution. The technical assistance of Mr, John Martens is also gratefully acknowledged.
PY - 1993/5/28
Y1 - 1993/5/28
N2 - Several peptides (cytokines), viz., interleukin-1 (IL-1), interferon-α (IFN-α), interleukin-6 (IL-6), tumor necrosis factor (TNF), are formed in response to conditions causing tissue inflammation or damage and are implicated in reactive changes of the host, including fever, while IL-1 has been considered an important mediator of fever, the other cytokines, specifically IL-6 and TNF, have recently acquired prominence. The present study extends earlier research on IL-6 and addresses the question of the role of IL-6 and TNF in the genesis of fever. Experiments were conducted in the conscious cat, and IL-6 and TNF were assayed concomitantly in cerebrospinal fluid (CSF) from the third ventricle using specific bioassays. In the absence of fever, IL-6 was usually below the threshold of the assay (4-32 pg/ml), while TNF appeared measurable (424±57 pg/ml) in most experiments. A single intravenous injection of endotoxin (bolus) or continuous infusion of IL-1 at doses eliciting a sustained fever increased CSF levels of IL-6, but had no effect on concentrations of TNF. Intracerebroventricular injection of a pyrogenic dose of endotoxin led to an elevation of TNF and IL-6 and, in either case, the effect was manifest during the latent period before the fever. In addition, by the same route, IL-1 caused a rise in IL-6. We conclude that brain is intrinsically capable of producing both IL-6 and TNF depending on the site of challenge. However, since IL-6 CSF levels are elevated regardless of the site of pyrogen injection, IL-6 lends itself better to a role in the pathogenesis of fever.
AB - Several peptides (cytokines), viz., interleukin-1 (IL-1), interferon-α (IFN-α), interleukin-6 (IL-6), tumor necrosis factor (TNF), are formed in response to conditions causing tissue inflammation or damage and are implicated in reactive changes of the host, including fever, while IL-1 has been considered an important mediator of fever, the other cytokines, specifically IL-6 and TNF, have recently acquired prominence. The present study extends earlier research on IL-6 and addresses the question of the role of IL-6 and TNF in the genesis of fever. Experiments were conducted in the conscious cat, and IL-6 and TNF were assayed concomitantly in cerebrospinal fluid (CSF) from the third ventricle using specific bioassays. In the absence of fever, IL-6 was usually below the threshold of the assay (4-32 pg/ml), while TNF appeared measurable (424±57 pg/ml) in most experiments. A single intravenous injection of endotoxin (bolus) or continuous infusion of IL-1 at doses eliciting a sustained fever increased CSF levels of IL-6, but had no effect on concentrations of TNF. Intracerebroventricular injection of a pyrogenic dose of endotoxin led to an elevation of TNF and IL-6 and, in either case, the effect was manifest during the latent period before the fever. In addition, by the same route, IL-1 caused a rise in IL-6. We conclude that brain is intrinsically capable of producing both IL-6 and TNF depending on the site of challenge. However, since IL-6 CSF levels are elevated regardless of the site of pyrogen injection, IL-6 lends itself better to a role in the pathogenesis of fever.
KW - Blood-brain barrier
KW - Endotoxin
KW - Fever mechanism
KW - Interleukin-1
KW - Interleukin-6
KW - Tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=0027299855&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(93)91657-E
DO - 10.1016/0006-8993(93)91657-E
M3 - Artículo
SN - 0006-8993
VL - 612
SP - 165
EP - 171
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -