Hyperresponsive febrile reactions to interleukin (IL) 1α and IL-1β, and altered brain cytokine mRNA and serum cytokine levels, in IL-1β-deficient mice

Abstract

IL-1␤ is an endogenous pyrogen that is induced during systemic lipopolysaccharide (LPS)-or IL-1-induced fever. We have examined the fever and cytokine responses following i.p. injection of IL-1 agonists, IL-1␣ and IL-1␤, and compared these with response to LPS (i.p.) in wild-type and IL-1␤-deficient mice. The IL-1␤ deficient mice appear to have elevated body temperature but exhibit a normal circadian temperature cycle. Exogenously injected IL-1␤, IL-1␣, or LPS induced hyperresponsive fevers in the IL-1␤-deficient mice. We also observed phenotypic differences between wild-type and IL-1␤-deficient mice in hypothalamic basal mRNA levels for IL-1␣ and IL-6, but not for IL-1␤-converting enzyme or IL-1 receptor type I or type II. The IL-1␣ mRNA levels were down-regulated, whereas the IL-6 mRNA levels were up-regulated in the hypothalamus of IL-1␤-deficient mice as compared with wild-type mice. The IL-1␤-deficient mice also responded to LPS challenge with significantly higher serum corticosterone and with lower serum tumor necrosis factor type ␣ levels than the wild-type mice. The data suggest that, in the redundant cascade of proinf lammatory cytokines, IL-1␤ plays an important but not obligatory role in fever induction by LPS or IL-1␣, as well as in the induction of serum tumor necrosis factor type ␣ and corticosterone responses either by LPS or by IL-1␣ or IL-1␤.

Pattern of interleukin‐1β secretion in response to lipopolysaccharide and ATP before and after interleukin‐1 blockade in patients with CIAS1 mutations

“…In fact, the rapid clinical remission obtained in our patients was associated with a prompt decrease in IL-1␤ secretion by LPS-stimulated peripheral blood mono-3146 GATTORNO ET AL cytes, which strongly suggests that the monocytes themselves represent a major target of anakinra. This observation is consistent with previous studies highlighting the capacity of IL-1 to induce IL-1 itself (35)(36)(37). Anakinra can block this positive feedback, as confirmed by the observation that normal monocytes activated in vitro with LPS in the presence of recombinant IL-1Ra decrease IL-1␤ secretion (data not shown).…”

MK2 Targets AU-rich Elements and Regulates Biosynthesis of Tumor Necrosis Factor and Interleukin-6 Independently at Different Post-transcriptional Levels

“…Alterations in the serum level of IL-6 have been observed as a secondary effect, e.g. in mice lacking TNF (16) and IL-1␤ (17). To decide whether this is also the case in MK2…”

From the Golgi–Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: Wiring and volume transmission

“…Local microinjections of IL-1β into the neostriatum have given observations that striatal IL-1β exerts local and distant effects on microglial cells, and distant effects on paraventricular hypothalamic nerve cells, suggesting that IL-1β is a VT signal capable of long-distance diffusion and convection through the extracellular space and cerebrospinal fluid, acting on IL-1β receptors in the ependymal cells, the choroid plexus, the meninges and the brain capillaries , submitted for publication). Thus, locally formed IL-1β in the brain may via VT produce fever responses (Alheim et al, 1997) and pro-inflammatory events (Andersson et al, 1992), contributing to increases in blood-brain barrier permeability and leading to neuroimmune interactions (Anthony et al, 1997).…”