Expression of interleukin (IL)‐1β, IL‐6 and their respective receptors in the normal rat brain and after injury

Abstract

The expression of interleukin (IL)-1 beta, IL-6 and their respective receptors has been studied in the rat brain before and up to 24 h after injury. Messenger RNA transcripts of these four genes were detected by in situ hybridization (ISH) in different structures of the intact brain. The distribution was very similar for IL-1 beta, IL-6 and IL-6 receptor (IL-6R). The expression of IL-1R was more widespread. Within hours after injury, an increased expression of IL-1 beta, and thereafter of IL-6 was documented. The expression of IL-1R and IL-6R was also increased. This expression was bilateral and not restricted to the injured area. Within 24 h, all ISH patterns had returned to normal. The molecular data were confirmed by protein data. Indeed, the distribution of IL-6 (detected by immunocytochemistry) agreed with the ISH patterns for IL-6. Furthermore, extracellular fluid was collected by microdialysis at the site of the lesion during 12 h and successive fractions were assayed for the presence of bioactive IL-1 and IL-6. Increases in IL-1 and later in IL-6 levels were detected. The rapid and concomitant increased expression of IL-1 beta, IL-6 and their receptors after injury stresses their possible early role in inflammatory mechanisms also in the brain, before any recruitment of inflammatory cells from remote nervous and not nervous areas.

Experimental Axonal Injury Triggers Interleukin-6 mRNA, Protein Synthesis and Release into Cerebrospinal Fluid

“…However, IL-6 immunoreactivity revealed a weak constitutive produc tion in these areas of control brain, thus confirming ear-lier results at the mRNA level. The discre p ancy between our in situ hybridization findings and those reported by others may result from methodology, in this case immu nodetection of DIG-labeled p robes versus radioactively labeled ones (Yan et al, 1992;Schobitz et al, 1993), or p olymerase chain reaction from tissue extracts (Gadient and Otten, 1994a,b). Therefore, we regard cells exhibit ing positive staining as foci of an extremely upregulated transcription/decreased degradation of IL-6 mRNA.…”

Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent Pain

“…An elevation of IL-6 level in the brainstem, including the spinal trigeminal complex, is found after trigeminal nerve injury in the rat (Anderson and Rao, 2001). Different from the response to direct brain injury (Yan et al, 1992), the induction of central cytokines after peripheral injury involves more complicated and still unknown pathways at both spinal and trigeminal levels. Our results suggest that the proinflammatory cytokine IL-1␤ was selectively induced in astroglia in the Vi/Vc transition zone after inflammation.…”

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

“…More recent studies have revealed that this cytokine also arises from both the parenchyma and the fiber tracts (corpus callosum, anterior commissure, fimbria, lateral olfactory tract, optic tract, internal capsule, and corticospinal tracts within the caudate) of the CNS (Schobitz et al, 1993) and can be localized in several neuronal types including pyramidal and granular neurons of the hippocampus, neurons of the habenular nucleus, ventromedial and medial preoptic nuclei of the hypothalamus, cerebellar granular neurons, and pyramidal neurons of the cerebral cortex (Schobitz et al, 1993). Its presence in white matter suggests the expression of IL-6 by oligodendrocytes, the CNS cell type responsible for myelination of axons that comprise the fiber tracts (Yan et al, 1992).…”