Interleukin-1β (187-207)-induced hyperthermia is inhibited by interleukin-1β (193-195) in rats

Interleukin-1β (IL-1β) is a pro-inflammatory cytokine, which plays an important role in the immune response and signal transduction both in the periphery and the central nervous system (CNS). Various diseases of the CNS, including neurodegenerative disorders, vascular lesions, meningo-encephalitis or status epilepticus are accompanied by elevated levels of IL-1β. Different domains within the IL-lβ protein are responsible for distinct functions. The IL-lβ domain in position 208-240 has pyrogenic properties, while the domain in position 193-195 exerts anti-inflammatory effects. Previous studies provide little evidence about the effect of the domain in position 187-207 on the body temperature. Therefore, the aim of the present study was to investigate the action of IL-1β (187-207) and its interaction with IL-1β (193-195) on the body temperature. IL fragments were administered intracerebroventricularly and the body temperature was measured rectally in male Wistar rats. IL-1β (187-207) induced hyperthermia, while IL-1β (193-195) did not influence the core temperature considerably. In co-administration, IL-1β (193-195) completely abolished the IL-1β (187-207)-induced hyperthermia. The non-steroid anti-inflammatory drug metamizole also reversed completely the action of IL-1β (187-207). Our results provide evidence that the IL-lβ domain in position 187-207 has hyperthermic effect. This effect is mediated through prostaglandin E2 stimulation and other mechanisms may also be involved in the action of IL-1β (187-207). It also suggests that IL-lβ domain in position 187-207 and IL-1β (193-195) fragment may serve as novel target for treatment of disorders accompanied with hyperthermia.