Role of alpha 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 ( 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)-1 , IL-6, and tumor necrosis factor- (TNF- ). To define the role of 2 M in regulation of febrile and cytokine responses, wild-type mice and mice deficient in 2 M ( 2 M / ) 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 2 M / mice were compared with those in wild-type control mice. The 2 M / mice developed a short-term markedly attenuated (ANOVA, P