Interleukin-1-induced sleep and febrile responses differentially altered by a muramyl dipeptide derivative.

Abstract

Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine; AcMur-L-Ala-D-iGln; MDP) is a somnogenic, pyrogenic, and immunoadjuvant component of bacterial cell wall peptidoglycan. It enhances the production of the cytokine interleukin 1 (IL-1) in vivo and in vitro; IL-1 itself is somnogenic and pyrogenic. The pyrogenic effects of IL-1 may be separated from its somnogenicity by the use of antipyretics. A methyl ester derivative of MDP (murametide; AcMur-L-Ala-D-Gln-alpha-methyl ester) blocks IL-1-induced fever, but induces IL-1 production/release. Therefore, the effects of murametide on IL-1-induced sleep and fever responses were determined. Rabbits were pretreated with intravenous injections of murametide 0, 30 or 60 min before intravenous injection of a pyrogenic/somnogenic dose of recombinant IL-1 beta (rIL-1 beta). Murametide alone produced no effects on sleep or brain temperatures. Murametide given simultaneously with rIL-1 beta potentiated increases of brain temperatures, whereas when there was a 60 min delay between the injection of murametide and rIL-1 beta, responses were similar to those induced by rIL-1 beta alone. Murametide given 30 min before rIL-1 beta, blocked the expected IL-1-induced fevers but not the rIL-1 beta-mediated increases of slow-wave sleep and decreases of rapid-eye-movements sleep. These results reinforce the conclusion that, in part, independent brain mechanisms are involved in the somnogenic and pyrogenic actions of IL-1.

• Authors: A B Cady, G Riveau, L Chedid, C A Dinarello, L Johannsen, J M Krueger
• Journal: International journal of immunopharmacology (Int J Immunopharmacol) Vol. 11 Issue 8 Pg. 887-93 ( 1989) ISSN: 0192-0561 [Print] England
• PMID: 2613394 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Interleukin-1
• Pyrogens
• Acetylmuramyl-Alanyl-Isoglutamine
• N-acetylmuramyl-alanylglutamine methyl ester

Topics

• Acetylmuramyl-Alanyl-Isoglutamine (administration & dosage, analogs & derivatives, pharmacology)
• Adjuvants, Immunologic (pharmacology)
• Animals
• Drug Interactions
• Fever (chemically induced, prevention & control)
• Interleukin-1 (administration & dosage, antagonists & inhibitors, pharmacology)
• Male
• Pyrogens (pharmacology)
• Rabbits
• Sleep (drug effects)