Fever and feeding: Differential actions of macrophage inflammatory protein-1 (MIP-1), MIP-1? and MIP-1? on rat hypothalamus

Abstract

Changes in body temperature (Tb) and feeding were characterized in unrestrained rats following the micro-injection into the anterior hypothalamic preoptic area (AH/POA) of macrophage inflammatory protein-1 (MIP-1), MIP-1 alpha or MIP-1 beta. After the rats recovered from the stereotaxic implantation of a single guide tube placed in the AH/POA, either one of the MIP-1 compounds or control CSF was micro-injected in a volume of 1.0 microliter into this area. Changes in body temperature (Tb) and food and water intakes were monitored throughout each experiment. When micro-injected into the AH/POA in a dose of 28 or 280 pg, doublet MIP-1 and MIP-1 beta evoked a monophasic fever which increased above baseline to a mean maximum of 2.17 +/- 0.14 degrees C and 2.1 +/- 0.24 degrees C, respectively. MIP-1 alpha micro-injected similarly evoked a biphasic fever, with the Tb declining transiently at the 30 min point > or = 0.4 degrees C lower than the congruent rises in Tb evoked by doublet MIP-1 or MIP-1 beta. The secondary rise in Tb induced by MIP-1 alpha had a latency of 1.5-2.0 hrs and reached a maximum of 1.56 +/- 0.16 degrees C. Although all three cytokines significantly attenuated the rats' mean intake of food during the 24 hr interval after their micro-injection into the AH/POA, doublet MIP-1 exerted the most potent anorexic effect in comparison to that of the saline control rats. However, neither body weight nor intake of water was altered significantly by the three cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic interaction between macrophage inflammatory protein‐1 alpha (MIP‐1 alpha) and MIP‐1 beta in rats: a new level for fever control?

“…The present results, together with previous data, support a role for MIP-la and MIP-1l8 in the pathogenesis of fever and uphold the hypothesis that endogenously produced MIP-1 plays a role in the development of fever (Mifiano et al 1990;Mifiano et al 1991;Myers et al 1993). Previously, it was reported that native murine MIP-1, a mixture of the a and ,1 subunits, induced a febrile response in the rabbit and rat.…”

Chemokines and chemokine receptors in the brain: implication in neuroendocrine regulation

“…It was reported that these two chemokines present differences in their ability to induce hyperthermia. MIP-1b/CCL4 causes an immediate and sustained rise in the body temperature of the rat, whereas MIP-1a/CCL3 exerts a hyperthermic response with a longer latency and lower magnitude (Myers et al 1993, Minano et al 1996. Moreover, it was observed that the co-injection of MIP-1a/CCL3 and MIP-1b/CCL4 into the AH/POA attenuates the increase in body temperature by either chemokine injected alone (Minano et al 1996).…”

“…MIP-1a/CCL3 and MIP-1b/CCL4 are also involved in the control of food intake. Indeed, when they are directly injected in the rat ventromedial hypothalamus (a structure implicated in the inhibition of feeding behavior) or into the rat AH/POA, they decrease feeding (Minano & Myers 1991, Myers et al 1993. Moreover, it was reported in the rat that i.c.v.…”

Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes.

“…For example, MIP-la selectively attracts CD8+ lymphocytes and B cells, while MIP-1j3 recruits CD4+ lymphocytes (7,8). In addition to their lymphocyte chemotactic properties, both MIP-1 peptides are chemotactic for macrophages, both are potent pyrogens (9), and MIP-la (but not MIP-1 3) suppresses erythropoiesis (10). These profiles of bioactivity support the possibility that altered chemokine 13 peptide production may be important both to the natural history of HIV infection and to the development of HIV disease.…”

“…A marked difference in the location and number of cells positive for PCRamplified HIV-1 DNA in the tissues from patient 1 as compared with patient 2 is seen. In brain tissue samples from patient 1, many positive cells were evident in the gray matter, 5), HIV-infected patients without neurological symptoms (lanes [6][7][8][9], and uninfected control patients (lanes 10-12) and reverse-transcribed with random hexamer primers. tRepresentative photos of sections from this patient analyzed for MIP-la and MIP-1,B by in situ PCR can be seen in Fig.…”