THE USE OF KNOCKOUT MICE TO UNDERSTAND THE ROLE OF CYTOKINES IN FEVER

1. In most instances, data obtained using knockout mice to dissect the role of cytokines in fever are similar to data obtained by other, mor e traditional experimental techniques, 2. Interleukin (IL)-1 beta appe ars to be critically involved in fever caused by some routes of infect ion/inflammation (e.g. localized inflammation with turpentine), This c ytokine has only a small role in fevers caused by i.p. injection of li popolysaccharide (LPS), These IL-1 beta-induced fevers in knockout mic e appear to be via the induction of IL-6, similar to LPS-induced fever s in rats, Interleukin-6 also appears to be critically involved in tur pentine-induced fever, 3. The precise role of tumour necrosis factor ( TNF) in fever is controversial, Data obtained from knockout mice lacki ng both TNF receptors do not support a pyrogenic role for TNF in fever either to i.p. injection of LPS, s.c. injection of turpentine or foll owing caecal ligation and puncture, 4. The roles of these cytokines in fevers induced by injection of LPS, IL-1 beta, turpentine and caecal ligation and puncture are summarized, The data show the complexity of the febrile response, Depending on the types of inflammatory/infectiou s stimuli, different cytokines play important roles, Because other cyt okines are thought to be involved in fever (e.g. macrophage inflammato ry protein, interferons), considerable work is still needed to dissect the precise roles of cytokines in fever.