Macrophage inflammatory protein-1beta (MIP-1beta) produced endogenously in brain during E. coli fever in rats. 1996

F J Miñano, and A Fernández-Alonso, and K Benamar, and R K Myers, and M Sancibrián, and R M Ruiz, and J A Armengol
Departamento de Farmacologia, Pediatría y Radiología, Facultad de Medicina, Universidad de Sevilla, Avda. Sánchez Pizjuan 4, 41009 Sevilla, Spain.

Macrophage inflammatory protein-1 (MIP-1) evokes an intense fever, independent of a prostaglandin mechanism, and is now thought to play an important role in the defence response to bacterial pyrogens. The purpose of this study was 2-fold: (i) to determine whether the potent doublet of this cytokine, MIP-1beta, is actually produced in the brain in response to a pyrogenic dose of a lipopolysaccharide of Escherichia coli and (ii) to determine the anatomical site of synthesis of this cytokine in the brain. Following the intense fever produced by intraperitoneal administration of lipopolysaccharide in the unrestrained rat, MIP-1beta immunoreactivity was identified post mortem in two regions of the brain implicated in fever: the organum vasculosum laminae terminalis (OVLT) and the anterior hypothalamic, preoptic area (AH/POA). Microinjection of goat anti-mouse MIP-1beta antibody (anti-MIP-1beta) directly int the AH/POA markedly suppressed fever in rats in response to lipopolysaccharide. Further anti-MIP-1beta administered 180 min after the injection of lipopolysaccharide acted as an antipyretic and reversed the fever induced by the endotoxin. anti-MIP-1beta or control immunoglobulin G antibody microinjected into the hypothalamus immediately before the intraperitoneal injection of the control saline did not alter the temperature of the rats. Taken together, the present results demonstrate that MIP-1beta is produced in the brain in response to a bacterial endotoxin. These observations, in the light of earlier data on fever induced by MIP-1beta, further support the hypothesis that endogenously synthesized MIP-1beta acts as an intermediary factor in the evocation of fever by acting on the thermosensitive cells of the brain.

UI MeSH Term Description Entries
D007032 Hypothalamus, Anterior The front portion of the HYPOTHALAMUS separated into the preoptic region and the supraoptic region. The preoptic region is made up of the periventricular GRAY MATTER of the rostral portion of the THIRD VENTRICLE and contains the preoptic ventricular nucleus and the medial preoptic nucleus. The supraoptic region contains the PARAVENTRICULAR HYPOTHALAMIC NUCLEUS, the SUPRAOPTIC NUCLEUS, the ANTERIOR HYPOTHALAMIC NUCLEUS, and the SUPRACHIASMATIC NUCLEUS. Hypothalamus, Supraoptic,Anterior Hypothalamic Commissure,Anterior Hypothalamic Decussation of Ganser,Anteroventral Periventricular Nucleus,Anterior Hypothalamic Commissures,Anterior Hypothalamus,Commissure, Anterior Hypothalamic,Commissures, Anterior Hypothalamic,Hypothalamic Commissure, Anterior,Hypothalamic Commissures, Anterior,Nucleus, Anteroventral Periventricular,Periventricular Nucleus, Anteroventral,Supraoptic Hypothalamus
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008297 Male Males
D008845 Microinjections The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes. Microinjection
D011301 Preoptic Area Region of hypothalamus between the ANTERIOR COMMISSURE and OPTIC CHIASM. Area Preoptica,Lateral Preoptic Area,Medial Preoptic Area,Preoptic Nuclei,Area Preopticas,Area, Lateral Preoptic,Area, Medial Preoptic,Area, Preoptic,Areas, Lateral Preoptic,Areas, Medial Preoptic,Areas, Preoptic,Lateral Preoptic Areas,Medial Preoptic Areas,Nuclei, Preoptic,Nucleus, Preoptic,Preoptic Area, Lateral,Preoptic Area, Medial,Preoptic Areas,Preoptic Areas, Lateral,Preoptic Areas, Medial,Preoptic Nucleus,Preoptica, Area,Preopticas, Area
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D004731 Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Endotoxin
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D005334 Fever An abnormal elevation of body temperature, usually as a result of a pathologic process. Pyrexia,Fevers,Pyrexias

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