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Fever induced by macrophage inflammatory protein-1 (MIP-1) in rats: hypothalamic sites of action
F J Miñano1, M Sancibrian, R D Myers
1Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
Abstract:
The purpose of this study was to clarify the central site of action as well as functional characteristics of the febrile response of the cytokine, macrophage inflammatory protein-1 (MIP-1). Guide cannulae for microinjection were implanted stereotaxically in the rat just above the pyrogen and thermosensitive area of the anterior hypothalamic, preoptic area (AH/POA). Following postoperative recovery, the body temperature of each rat (Tbo) was monitored during an experiment by a colonic thermistor probe at 0.5-1.0-h intervals. When MIP-1 was microinjected in a 0.5-microliter volume into the AH/POA in one of eight concentrations ranging from 0.0028 nanograms (ng) to 9.0 ng, an intense monophasic or biphasic fever was evoked. The MIP-1-induced increase in the Tbo of the rat was characterized by its short latency of 15 to 30 min and an inverse dose-response curve. Measures of mean latency and maximal rise in Tbo following MIP-1 confirmed the potency of this dose. Although the dose of 0.028 ng produced a fever of over 2.0 degrees C with a latency of only 15 min or less, the hyperthermic response became less intense as the dose of MIP-1 was increased. An anatomical mapping of sites of microinjection which reacted to MIP-1 in mediating fever revealed that the medial portion of the POA of the rat just rostral to the border of the AH was the region of maximum sensitivity to the cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Macrophage inflammatory protein-1 (MIP-1) induces fever when injected into the anterior hypothalamic, preoptic area (AH/POA) in rats. This cytokine
Area of Science:
- Neuroscience
- Immunology
- Physiology
Background:
- Cytokines play a role in regulating body temperature and fever responses.
- Macrophage inflammatory protein-1 (MIP-1) is a cytokine implicated in inflammatory processes.
Purpose of the Study:
- To determine the specific brain region responsible for MIP-1-induced fever.
- To characterize the functional properties of MIP-1's fever response.
Main Methods:
- Stereotaxic surgery to implant guide cannulae in the rat's anterior hypothalamic, preoptic area (AH/POA).
- Microinjection of varying concentrations of MIP-1 into the AH/POA.
- Continuous monitoring of rat body temperature (Tbo) using a colonic thermistor probe.
Main Results:
- MIP-1 microinjection into the AH/POA evoked intense monophasic or biphasic fevers.
- The fever response exhibited a short latency (15-30 min) and an inverse dose-response relationship.
- The medial portion of the POA, adjacent to the AH, was identified as the most sensitive site for MIP-1's pyrogenic effect.
Conclusions:
- The anterior hypothalamic, preoptic area (AH/POA) is a critical site for MIP-1-induced fever.
- MIP-1 acts as a potent pyrogen with specific characteristics in its fever induction.
- The medial POA is the primary target region for MIP-1's thermoregulatory effects.