HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Aronoff, D. M. Search for Related Content PubMed PubMed Citation Articles by Aronoff, D. M.

---

COMMENT

Comments to the Editor Concerning the Paper Entitled ``Orexin-A Regulates Body Temperature in Coordination with Arousal Status'' by Yoshimichi et al.

Divisions of Infectious Diseases and Clinical Pharmacology and the Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232

Maintenance of normal body temperature (thermoregulation) involves an integrated network of neural connections involving the hypothalamus, limbic system, lower brainstem, the reticular formation, spinal cord, and the sympathetic ganglia (1). The recent work by Yoshimichi et al. in the May issue of Experimental Biology and Medicine suggests that orexins play a role in the central control of thermogenesis (2). The results indicate that orexin-A injected into the third cerebroventricle provokes a rise in ambulatory activity followed by a sustained increase in core body temperature. It is not clear, however, if the elevated temperature results from a direct effect of orexin-A upon hypothalamic neurons bearing orexin receptors or results from a secondary, pyrogenic effect of the injected neuropeptide.

The preoptic area of the anterior hypothalamus (POAH) is believed to be the critical thermoregulatory site within the central nervous system for coordinating a febrile response following appropriate pyrogenic stimuli (3). Prostaglandin E₂ (PGE₂) produced within the POAH is responsible for provoking thermoregulatory neurons to induce fever (reviewed in [4]). PGE₂ production is stimulated by endogenous pyrogenic cytokines such as interleukin-1 and interleukin-6 (reviewed in (5)) and exogenous pyrogenic substances such as lipopolysaccharide (6). In addition, inhibitors of the prostaglandin-generating enzyme cyclooxygenase can suppress fever following exposure to pyrogens (7).

It is difficult to tell from the study by Yoshimichi et al. whether intracerebroventricular injection of orexin-A may be inducing fever through the stimulation of PGE₂ within the POAH. A reasonable control experiment might sort this out. For instance, administration of a cyclooxygenase inhibitor (such as indomethacin) to the rats prior to treatment with orexin-A would be expected to prevent or suppress the subsequent elevation in body temperature if PGE₂ were involved. Also helpful would be measurement of cerebrospinal fluid PGE₂ following orexin-A (and phosphate-buffered saline) in the presence or absence of the cyclooxygenase inhibitor. Cerebrospinal fluid levels of PGE₂ generally mimic changes in core body temperature in animals experiencing pyrogen-induced fever (6). Demonstrating that the rise in temperature seen after orexin-A injection is independent of PGE₂-mediated pyrogenesis would further support the important data presented by Yoshimichi et al. implicating orexins as possible mediators of circadian thermoregulation.

Footnotes

We welcome comments by our readers reflecting agreement or disagreement with the material published in this section and, at the discretion of the Editor-in-Chief, will publish such comments.

¹ To whom requests for reprints should be addressed at Division of Clinical Pharmacology, 514 RRB, 23^rd Avenue at Pierce, Nashville, TN 37232-6603. E-mail: David.aronoff{at}mcmail.vanderbilt.edu

References

1. Boulant JA. Thermoregulation. In: Mackowiak PA, Ed. Fever: Basic mechanisms and management. Philadelphia: Lippincott-Raven, pp35–58, 1997.
2. Yoshimichi G, Yoshimatsu H, Masaki T, Sakata T. Orexin-A regulates body temperature in coordination with arousal status. Exp Biol Med 226:468–476, 2001.[Abstract/Free Full Text]
3. Aronoff DM, Neilson EG. Antipyretics: Mechanisms of action and clinical use in fever suppression. Am J Med 111:304–315, 2001.[Medline]
4. Blatteis CM, Sehic E. Prostaglandin E₂: A putative fever mediator. In: Mackowiak PA, Ed. Fever: Basic mechanisms and management. Philadelphia: Lippincott-Raven, pp117–145, 1997.
5. Dinarello CA. Cytokines as endogenous pyrogens. J Infect Dis 179(Suppl 2):S294–S304, 1999.
6. Sehic E, Szekely M, Ungar AL, Oladehin A, Blatteis CM. Hypothalamic prostaglandin E2 during lipopolysaccharide-induced fever in guinea pigs. Brain Res Bull 39:391–399, 1996.[Medline]
7. Feldberg W, Gupta KP, Milton AS, Wendlandt S. Effect of bacterial pyrogen and antipyretics on prostaglandin activity in cerebrospinal fluid of unanaesthetized cats. Br J Pharmacol 46:550P–551P, 1972.[Medline]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Aronoff, D. M. Search for Related Content PubMed PubMed Citation Articles by Aronoff, D. M.