Lipopolysaccharide-induced fever is dissociated from apoptotic cell death in the rat brain

Immune system activation induces increase in expression level and enzymatic activity of interleukin-1 beta converting enzyme (ICE) in rat brain. As ICE has been implicated in apoptotic cell death, a possible link may exist between immune system activation by bacterial endotoxic lipopolysaccharide (LPS) and apoptosis in rat brain. The aim of this study was to investigate possible effect of acute (5.5 h) or chronic (5 days) intraperitoneal (i.p.) administration and central injection of LPS on brain apoptotic cell death. Body temperature was continuously monitored for fever, a hallmark of immune activation. Detection of apoptotic cell death was carried out by using in situ labelling of DNA fragmentation in various brain structures. Despite the chronic or the acute pyrogenic effects of LPS, no evidence for apoptotic cell death was observed in any of the brain areas analysed, including hippocampus, hypothalamus, area postrema, subfornical organ, organum vasculosum of the lamina terminalis and nucleus tractus solitaris. Other well-known sites of apoptotic cell death, including brain of ischemic rat, mammary gland of post-lactating rat and rat intestine as well as Dnase-treated rat brain slices, were used as positive controls. These results suggest that ICE activation during fever development is dissociated from cell death by apoptosis in rat brain. Unlike peripheral targets of immunocompetent cytokines, a protective system, yet to be defined, may be present in the central nervous system and block the deleterious effects of infectious agents and cytokines.