Interleukin-1-induced sleep and febrile responses differentially altered by a muramyl dipeptide derivative.
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.
Cady
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AB
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
Riveau
G
G
Chedid
L
L
Dinarello
C A
CA
Johannsen
L
L
Krueger
J M
JM
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D005334:Fever / Q000139:chemically induced* / Q000517:prevention & control; D007375:Interleukin-1 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D011749:Pyrogens / Q000494:pharmacology; D011817:Rabbits; D012890:Sleep / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D011749:Pyrogens; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C042628:N-acetylmuramyl-alanylglutamine methyl ester