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Title: Role of alpha(2)-macroglobulin in fever and cytokine responses induced by lipopolysaccharide in mice
Authors: Gourine, Alexander V ×
Gourine, Valery N
Tesfaigzi, Yohannes
Caluwaerts, Nathalie
Van Leuven, Freddy
Kluger, Matthew J #
Issue Date: Jul-2002
Series Title: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology vol:283 issue:1 pages:R218-26
Abstract: Alpha(2)-macroglobulin (alpha(2)M) is not only a proteinase inhibitor in mammals, but it is also a specific cytokine carrier that binds pro- and anti-inflammatory cytokines implicated in fever, including interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). To define the role of alpha(2)M in regulation of febrile and cytokine responses, wild-type mice and mice deficient in alpha(2)M (alpha(2)M -/-) were injected with lipopolysaccharide (LPS). Changes in body temperature as well as plasma levels of IL-1beta, IL-6, and TNF-alpha and hepatic TNF-alpha mRNA level during fever in alpha(2)M -/- mice were compared with those in wild-type control mice. The alpha(2)M -/- mice developed a short-term markedly attenuated (ANOVA, P < 0.05) fever in response to LPS (2.5 mg/kg ip) compared with the wild-type mice. At 1.5 h after injection of LPS, the plasma concentration of TNF-alpha, but not IL-1beta or IL-6, was significantly lower (by 58%) in the alpha(2)M -/- mice compared with their wild-type controls (ANOVA, P < 0.05). There was no difference in hepatic TNF-alpha mRNA levels between alpha(2)M -/- and wild-type mice 1.5 h after injection of LPS. These data support the hypotheses that 1) alpha(2)M is important for the normal development of LPS-induced fever and 2) a putative mechanism of alpha(2)M involvement in fever is through the inhibition of TNF-alpha clearance. These findings indicate a novel physiological role for alpha(2)M.
URI: 
ISSN: 0363-6119
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Genetics and Transgenesis (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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