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Fever and feeding in the rat: Actions of intrahypothalamic interleukin‐6 compared to macrophage inflammatory protein‐1β (MIP‐1β)
Author(s) -
Myers R. D.,
LopezValpuesta F. J.,
Minñano F. J.,
Wooten M. H.,
Barwick V. S.,
Wolpe S. D.
Publication year - 1994
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490390105
Subject(s) - macrophage inflammatory protein , recombinant dna , chemokine , beta (programming language) , pathogenesis , inflammation , chemistry , medicine , endocrinology , biology , immunology , biochemistry , gene , computer science , programming language
The chemokines, macrophage inflammatory protein‐1 (MIP‐1) and its subunit MIP‐1β, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre‐optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (T b ) of MIP‐1β with that of interleukin‐6 (IL‐6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro‐injections, radio transmitters which monitor T b continuously were inserted intraperitoneally in each of 15 male Sprague‐Dawley rats. Each micro‐injection was made in a site in the AH/POA in a volume of 1.0 μl of pyrogen‐free artificial CSF, recombinant murine MIP‐1β, or recombinant human IL‐6. MIP‐1β in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in T b of 2.4 ± 0.21°C reached by 3.7 ± 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL‐6 induced a dose dependent fever of similar latency and a mean maximal increase in T b of 1.2 ± 0.25°C, 1.8 ± 0.15°C, and 2.1 ± 0.22°C and duration of 6.2 ± 1.28 hr, 6.7 ± 0.49 hr, and 6.8 ± 0.65 hr when given in doses of 25, 50, and 100 ng, respectively. These results show that MIP‐1β and the highest dose of IL‐6 induce a fever of comparable intensity, but MIP‐1β exerts its action in a much lower concentration. Thus, the de novo synthesis and subsequent action of the MIP‐1 family of cytokines on neurons of the AH/POA in response to a pyrogen challenge apparently play a functional role in the pathogenesis of fever. Further, the endogenous activity of IL‐6 in the hypothalamus which is enhanced in response to a lipopolysaccharide also may reflect its essential part in the acute phase response to a bacterial challenge. Copyright © 1994 Wiley‐Liss, Inc.