Behavioural pyrogenic and electrocortical effects of cytokines

Abstract

The behavioural and electrocortical (ECoG) effects of human recombinant tumor necrosis factor-α (hrTNF-α) and various forms of interleukin-1 (IL-1) microinjected into the locus coeruleus (LC) of rats were studied. IL-1 induced a typical, dose-dependent, behavioural sedation and/or sleep which was associated with ECoG synchronization. IL-Iβ appeared more potent than IL-1α. During sleep induced by the various forms of IL-1 a dose-dependent increase in total voltage power (0.25–16 Hz) as well as in the 3–6, 6–9 and sometimes 0.25–3 Hz frequency bands was observed. The behavioural and ECoG effects of IL-1β were blocked in rats pretreated with anti-IL-1 monoclonal antibodies. The microinjection of hrTNF-α into the LC produced a typical pattern characterized by a first short lasting (20–30 min) phase of behavioural arousal and ECoG desynchronization, followed by a longer lasting (45–80 min) phase of behavioural sedation and/or sleep and ECoG synchronization characterized by an increase in total voltage power as well as in the 3–6, 6–9 and sometimes 0.25–3 Hz frequency bands. The behavioural and ECoG effects of hrTNF-α were antagonized by a pretreatment (15 min before) with specific anti-TNF-α polyclonal antibodies. In addition, a pretreatment with anti-IL-1 receptor monoclonal antibodies was unable to significantly affect the stimulation of behaviour and ECoG desynchronization effects elicited by hrTNF-α whilst the same pretreatment completely prevent the sedative and ECoG synchronizing phase elicited by the microinjection of hrTNF-α into the LC. These results are consisted with the hypothesis that the sedative and/or soporific behavioural and ECoG changes of hrTNF-α are mediated, at LC level, through a local IL-1 release.