Blockade by interleukin-1 receptor antagonist of IL-1 beta-induced neuronal activity in guinea pig preoptic area slices.
Interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) are thought to be endogenous pyrogens, i.e., to mediate fever production; warm-sensitive (W) and cold-sensitive (C) neurons in the preoptic area (POA) are presumed to be the ultimate targets of endogenous pyrogens. The recent purification of an IL-1 receptor antagonist (IL-1ra) has provided a means for verifying the presumptive action of IL-1 on these neurons. This study was undertaken, therefore, to investigate whether IL-1ra may block the IL-1 alpha and IL-1 beta effects on the firing rates (FR) of W and C neurons in guinea pig POA slices. Human recombinant (hr) IL-1 beta (500 ng/ml) reduced the FR of 26 W neurons and increased those of 3 C neurons recorded; it had no effect on 8 thermally insensitive neurons. hrIL-1 alpha (200-600 ng/ml) did not change the FR of any neuron. IL-Ira (0.01-0.5 mg/ml) had no effect by itself on the FR of all the neurons, but it blocked the hrIL-1 beta-induced FR changes of 24 of the 26 W and of all 3 C neurons when given before the cytokine. The lowest effective dose was 0.05 mg/ml. These results support the hypothesis, therefore, that POA thermosensitive neurons may be direct targets of IL-1 beta and that it may be an endogenous pyrogen acting on these units to induce fever production.
Xin
L
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Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
Blatteis
C M
CM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011301:Preoptic Area / Q000502:physiology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins