Intracerebroventricular injection of interleukin 1 induces high circulating levels of interleukin 6.

Abstract

There is a growing interest for connections between the central nervous system (CNS) and systemic immune and/or inflammatory responses. The inflammatory cytokine IL-1 has a wide spectrum of targets, which include the CNS. Intracerebroventricular as well as systemic administration of IL-1 were reported to induce central effects including fever (1), slow-wave sleep (2), anorexia (3), and activation of the hypothalamus-pituitary axis leading to release of adrenal corticosteroids (4, 5). Moreover, different brain cells such as astrocytes, microglia, and neurons can respond and/or have been found to contain various cytokines like IL-1, IL-2, IL-6, and TNF, and there is evidence that these factors act on neuronal survival, growth, and differentiation (1, 3, 6-10).It is also possible that some of the systemic activities of IL-1 are, at least in part, centrally mediated . In fact, early reports indicated that central administration of crude leukocytic endogenous mediators (presumably containing, among other cytokines, IL-1) induced an increase of acute-phase proteins (11) . The mechanism by which centrally administered IL-1 can activate the synthesis of hepatic acute-phase proteins is still unknown, and the present study was aimed at revisiting this early observation by investigating how intracerebroventricularly administered rIL-1 induced a systemic response. Our attention was focused on IL-6, since this cytokine, induced by IL-1, plays a crucial role in the acute-phase response as a hepatocyte-stimulating factor, and the levels of circulating IL-6 were reported to correlate with the levels of acute-phase proteins in some infective and inflammatory diseases (12)(13)(14).

Opposing effects of pituitary leukemia inhibitory factor and SOCS-3 on the ACTH axis response to inflammation

“…Thus an acute inflammatory response during endotoxemia is mediated by induction of proinflammatory cytokines such as TNF-␣ (19,28). Subsequently, TNF-␣ induces IL-1␤ (18), which in turn, stimulates IL-6 synthesis and secretion (17). LIF decreased serum TNF-␣ concentrations in vivo (38) and in vitro (43).…”

Interferon-γ Potentiates Interleukin (IL)-6 and Tumor Necrosis Factor-α But Not IL-1β Induced by Endotoxin in the Brain

“…IL-6 was measured in CSF and in serum as hybridoma growth factor using the 7TD1 as previously described (29). Results are expressed as units/ml in comparison with a reference curve obtained in each experiment using recombinant human IL-6 (Immunex, Seattle, WA).…”

Increased production of inflammatory cytokines in mild cognitive impairment

“…However, it is unclear whether circulating amyloid is deposited in the brain and causes neuroinflammation or immune activation to abnormal amyloid peptide in the brain then triggers the peripheral immune response (Reale et al, 2005). Inflammatory signaling pathways exist from the brain to the periphery, but the mechanism of induction is unknown (De Simoni et al, 1990Gottschall et al, 1992;Song et al, 1999).…”