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2-macroglobulin in fever and cytokine
responses induced by lipopolysaccharide in mice
1 Institute of Physiology, National Academy of Sciences of Belarus, Minsk 220725, Belarus; 2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185; 3 Experimental Genetics Group, Department of Human Genetics, K. U. Leuven-Campus Gasthuisberg ON 06, B-3000 Leuven, Belgium; and 4 Medical College of Georgia, Augusta, Georgia 30912
2-Macroglobulin
(2M) 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)-1
, IL-6, and tumor necrosis factor- (TNF-). To define the
role of 2M in regulation of febrile and cytokine responses, wild-type mice and mice deficient in 2M
(2M 
/) were injected with lipopolysaccharide (LPS).
Changes in body temperature as well as plasma levels of IL-1, IL-6,
and TNF- and hepatic TNF- mRNA level during fever in
2M / mice were compared with those in wild-type
control mice. The 2M / 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-,
but not IL-1 or IL-6, was significantly lower (by 58%) in the
2M / mice compared with their wild-type controls
(ANOVA, P < 0.05). There was no difference in hepatic
TNF- mRNA levels between 2M / and wild-type mice
1.5 h after injection of LPS. These data support the hypotheses
that 1) 2M is important for the normal development of LPS-induced fever and 2) a putative mechanism
of 2M involvement in fever is through the inhibition of
TNF- clearance. These findings indicate a novel physiological role
for 2M.
thermoregulation; proteinase inhibitor; interleukin; tumor necrosis factor; endotoxin
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