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.