Interleukin 1 receptor antagonist blocks somnogenic and pyrogenic responses to an interleukin 1 fragment

M. R. Opp, Arnold Postlethwaite, J. M. Seyer, J. M. Krueger

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Abstract

Previously it was shown that human interleukin 1 (huIL-1) and a huIL-1 fragment, huIL-1β208-240, are somnogenic and pyrogenic in rabbits. However, the amino acid sequences for IL-1 are species-specific and it was unknown whether rabbit (rb) IL-1β208-240 and rat (rt) IL-1β208-240 were active in their respective species. Furthermore, it was unknown whether these fragments elicited their effects via the IL-1 receptors. Two doses of rbIL-1β208-240 (6.0 and 12.0 nmol) were intracerebroventricularly administered to rabbits. The 6.0-nmol dose had little effect, whereas the 12.0-nmol dose greatly increased non-rapid-eye-movement sleep across a 6-hr recording period and induced a febrile response. Rats injected intracerebroventricularly with rtIL-1β208-240 at dark onset responded to three doses of the peptide (1.2, 2.4, and 4.8 nmol). The 1.2-nmol dose did not greatly affect sleep but did induce a moderate febrile response. The 2.4- and 4.8-nmol doses increased non-rapid-eye-movement sleep across the 12-hr recording period. Maximal brain temperature elevations relative to controls after the 2.4- and 4.8-nmol doses of the peptide were 0.9 ± 0.2°C and 0.7 ± 0.2°C, respectively. These responses in both rabbits and rats were completely blocked or significantly attenuated when the animals were pretreated with an IL-1 receptor antagonist. These results suggest that the biological activities of IL-10208-240 are mediated via the IL-1β receptors.

Original languageEnglish (US)
Pages (from-to)3726-3730
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number9
DOIs
StatePublished - Jan 1 1992

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Interleukin-1 Receptors
Interleukin-1
Rabbits
Sleep
Eye Movements
Fever
Peptides
Amino Acid Sequence
Temperature
Brain

All Science Journal Classification (ASJC) codes

  • General

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Interleukin 1 receptor antagonist blocks somnogenic and pyrogenic responses to an interleukin 1 fragment. / Opp, M. R.; Postlethwaite, Arnold; Seyer, J. M.; Krueger, J. M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 9, 01.01.1992, p. 3726-3730.

Research output: Contribution to journalArticle

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