Interleukin 1 receptor antagonist blocks somnogenic and pyrogenic responses to an interleukin 1 fragment.
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.
Opp
M R
MR
Department of Physiology, University of Tennessee, Memphis 38163.
Postlethwaite
A E
AE
Seyer
J M
JM
Krueger
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000502:physiology; D016384:Consensus Sequence; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D011749:Pyrogens; D011817:Rabbits; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D012890:Sleep / Q000187:drug effects*; D013997:Time Factors
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D010455:Peptides; D011506:Proteins; D011749:Pyrogens; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins