LIPOPOLYSACCHARIDE-INDUCED FEVER IS DISSOCIATED FROM APOPTOTIC CELL-DEATH IN THE RAT-BRAIN

Immune system activation induces increase in expression level and enzy matic activity of interleukin-l beta converting enzyme (ICE) in rat br ain. As ICE has been implicated in apoptotic cell death, a possible li nk may exist between immune system activation by bacterial endotoxic l ipopolysaccharide (LPS) and apoptosis in rat brain. The aim of this st udy was to investigate possible effect of acute (5.5 h) or chronic (5 days) intraperitoneal (i.p.) administration and central injection of L PS on brain apoptotic cell death. Body temperature was continuously mo nitored for fever, a hallmark of immune activation. Detection of apopt otic cell death was carried out by using in situ labelling of DNA frag mentation in various brain structures. Despite the chronic or the acut e pyrogenic effects of LPS, no evidence for apoptotic cell death was o bserved in any of the brain areas analysed, including hippocampus, hyp othalamus, area postrema, subfornical organ, organum vasculosum of the lamina terminalis and nucleus tractus solitaris. Other well-known sit es of apoptotic cell death, including brain of ischemic rat, mammary g land of post-lactating rat and rat intestine as well as Dnase-treated rat brain slices, were used as positive controls. These results sugges t that ICE activation during fever development is dissociated from cel l death by apoptosis in rat brain. Unlike peripheral targets of immuno competent cytokines, a protective system, yet to be defined, may be pr esent in the central nervous system and block the deleterious effects of infectious agents and cytokines. (C) 1998 Elsevier Science B.V. All rights reserved.