Differential sensitivities of pyrogenic chemokine fevers to CC chemokine receptor 5 antibodies
| Autor: | Francisco J. Miñano, Eva Tavares |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Chemokine Time Factors Fever Microinjections Receptors CCR5 Antibodies Body Temperature Heating Stereotaxic Techniques Pathogenesis Internal medicine medicine Animals Pharmacology (medical) Rats Wistar Chemokine CCL4 Chemokine CCL5 Macrophage inflammatory protein Microinjection Cerebrospinal Fluid Pharmacology biology Pyrogens Macrophage Inflammatory Proteins Preoptic Area Recombinant Proteins Rats Preoptic area Endocrinology Hypothalamus Chemokines CC Immunoglobulin G CCR5 Receptor Antagonists Immunology biology.protein Antibody CC chemokine receptors |
| Zdroj: | Fundamental and Clinical Pharmacology. 18:163-169 |
| ISSN: | 1472-8206 0767-3981 |
| DOI: | 10.1111/j.1472-8206.2003.00227.x |
| Popis: | Macrophage inflammatory protein (MIP)-1beta and RANTES (regulated on activation, normal T-cells expressed and secreted) are members of the CC-family of chemokines. Although these two peptides are structurally and functionally related to one another, each exhibits distinct features, which allows it to independently regulate specific aspects of the host inflammatory response. They evoked intense and functionally different febrile responses when applied directly on pyrogen-sensitive cells located in the in the preoptic area of the anterior hypothalamus (POA). The present experiments were carried out to test the central role of CCR5, a functional receptor for MIP-1beta and RANTES, in the febrile responses induced by these chemokines when injected directly into the POA. The microinjection of an equimolecular dose (50 pg) of either MIP-1beta or RANTES into the POA induced a rapid onset; monophasic fever in rats that persisted for a long period. The microinjection of 2.0 microg specific neutralizing antibodies against CCR5 (anti-CCR5) into the POA fails to affect the effects on body temperature induced by MIP-1beta. However, pretreatment with the same dose of anti-CCR5 suppressed the febrile response induced by RANTES given at the same site. The microinjection of control IgG or anti-CCR5 does not affect basal temperature, when administered alone at the same hypothalamic site. The present experiments show that hypothalamic CCR5 are functionally involved in the febrile response induced by RANTES, but not by MIP-1beta. They also suggest the existence of functionally different components in the presumptive primary locus of the thermoregulatory controller, in which both chemotactic cytokines, together other mediators, could play a relevant role in the complex process of fever pathogenesis. |
| Databáze: | OpenAIRE |
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