In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 290, No. 1 ( 2006-01), p. R180-R187
Abstract:
Macrophage-activating lipopeptide-2 (MALP-2) from Mycoplasma fermentans has been identified as a pathogen-associated molecular pattern of Mycoplasmas that causes activation of the innate immune system through the activation of the heterodimeric Toll-like receptors (TLRs)-2 and -6. The aim of this study was to characterize the ability of MALP-2 and a synthetic analog fibroblast-stimulating lipopeptide-1 (FSL-1; represents the NH 2 -terminal sequence of a lipoprotein from M. salivarium) to act as exogenous pyrogens, to induce formation of cytokines (endogenous pyrogens), and to cause sickness behavior, such as depressed motor activity, anorexia, and adipsia. For this purpose, body temperature, activity, food intake, and water intake were recorded for 3 days by use of telemetry devices in several groups of rats treated with MALP-2/FSL-1 or the respective control solutions. Intraperitoneal injections of FSL-1 caused fever at doses of 10 or 100 μg/kg, which was preceded by a pronounced phase of hypothermia in response to a dose of 1,000 μg/kg. The maximal fever (a peak of 1.5°C above baseline) was caused by the 100 μg/kg dose with almost identical responses to both MALP-2 and FSL-1. Fever was accompanied by pronounced rises of the proinflammatory cytokines TNF and IL-6 in plasma. Treatment with the TLR-2 and -6 agonists further induced a dose-dependent manifestation of anorexia and adipsia, as well as a reduction of motor activity. We could thus demonstrate that activation of TLR-2 and -6 can induce systemic inflammation in rats accompanied by the classical signs of brain-controlled illness responses.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.00579.2005
Language:
English
Publisher:
American Physiological Society
Publication Date:
2006
detail.hit.zdb_id:
1477297-8
SSG:
12
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