Fever and feeding in the rat: actions of intrahypothalamic interleukin-6 compared to macrophage inflammatory protein-1 beta (MIP-1 beta).
The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1 beta, 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 (Tb) of MIP-1 beta 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 Tb 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 microliter of pyrogen-free artificial CSF, recombinant murine MIP-1 beta, or recombinant human IL-6. MIP-1 beta in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in Tb of 2.4 +/- 0.21 degrees 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 Tb of 1.2 +/- 0.25 degrees C, 1.8 +/- 0.15 degrees C, and 2.1 +/- 0.22 degrees 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Myers
R D
RD
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
Lopez-Valpuesta
F J
FJ
Miñano
F J
FJ
Wooten
M H
MH
Barwick
V S
VS
Wolpe
S D
SD
D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000503:physiopathology; D001066:Appetite / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects; D054407:Chemokine CCL4; D016207:Cytokines / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage / Q000633:toxicity*; D019402:Macrophage Inflammatory Proteins; D008297:Male; D008845:Microinjections; D015846:Monokines / Q000008:administration & dosage / Q000633:toxicity*; D011301:Preoptic Area / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000633:toxicity; D013238:Stereotaxic Techniques
D054407:Chemokine CCL4; D016207:Cytokines; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011994:Recombinant Proteins