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

M R Opp; A E Postlethwaite; J M Seyer; J M Krueger

doi:10.1073/pnas.89.9.3726

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

Journal article

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

M R Opp, A E Postlethwaite, J M Seyer and J M Krueger

Proceedings of the National Academy of Sciences - PNAS, Vol.89(9), pp.3726-3730

05/01/1992

DOI: https://doi.org/10.1073/pnas.89.9.3726

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https://hdl.handle.net/2376/114500

PMCID: PMC525563

PMID: 1533282

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Abstract

Consensus Sequence

Amino Acid Sequence

Rabbits

Peptides - chemistry

Molecular Sequence Data

Rats

Pyrogens

Brain - physiology

Sleep - drug effects

Receptors, Immunologic - antagonists & inhibitors

Interleukin-1 - pharmacology

Peptides - pharmacology

Sialoglycoproteins

Animals

Time Factors

Body Temperature Regulation - drug effects

Interleukin 1 Receptor Antagonist Protein

Interleukin-1 - chemistry

Proteins - pharmacology

Interleukin-1 - antagonists & inhibitors

Receptors, Interleukin-1

Previously it was shown that human interleukin 1 (huIL-1) and a huIL-1 fragment, huIL-1 beta 208-240, 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-1 beta 208-240 and rat (rt) IL-1 beta 208-240 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-1 beta 208-240 (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-1 beta 208-240 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 degrees C and 0.7 +/- 0.2 degrees 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-1 beta 208-240 are mediated via the IL-1 beta receptors.

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Title: Interleukin 1 receptor antagonist blocks somnogenic and pyrogenic responses to an interleukin 1 fragment
Creators: M R Opp - Department of Physiology, University of Tennessee, Memphis 38163
A E Postlethwaite
J M Seyer
J M Krueger
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.89(9), pp.3726-3730
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: NS-25378 / NINDS NIH HHS
Identifiers: 99900547923901842
Language: English
Resource Type: Journal article