Role of the Cytokines in the Neuroendocrine-Immune System Axis

Spangelo, Bryan L.; Gorospe, William C.

doi:10.1006/frne.1995.1001

Cited by 112 publications

(63 citation statements)

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“…cytokines, nitric oxide, prostaglandins) into the CSF and brain parenchyma (Tsai et al, 1994;Svenungsson et al, 2001). Pro-inflammatory cytokines can also alter the stress hormone axis (Hayley et al, 2003;Hu et al, 1993;Rivest et al, 1992;Spangelo and Gorospe, 1995;Hansen and Krueger, 1997;Rivier and Rivest, 1993). More specifically, these cytokines are known to modulate immune responses and regulate corticosteroid levels through targeting glucocorticoid receptors in adrenal and the hypothalamic-pituitary glands (Del and Besedovsky, 2000;Lorton et al, 2003).…”

Section: Prelude To Cns Damage: Disruption Of the Blood-brain Barriermentioning

confidence: 99%

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Ballok

2007

Brain Research Reviews

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Animal models are extremely useful tools in defining pathogenesis and treatment of human disease. For many years researchers believed that structural damage to the brain of neuropsychiatric (NP) patients lead to abnormal mental function, but this possibility was not extensively explored until recently. Imaging studies of NP-systemic lupus erythematosus (SLE) support the notion that brain cell death accounts for the emergence of neurologic and psychiatric symptoms, and evidence suggests that it is an autoimmunity-induced brain disorder characterized by profound metabolic alterations and progressive neuronal loss. While there are a number of murine models of SLE, this article reviews recent literature on the immunological connections to neurodegeneration and behavioral dysfunction in the Fas-deficient MRL model of NP-SLE. Probable links between spontaneous peripheral immune activation, the subsequent central autoimmune/inflammatory responses in MRL/MpJ-Tnfrsf6 lpr (MRL-lpr) mice and the sequential mode of events leading to Fas-independent neurodegenerative autoimmune-induced encephalitis will be reviewed. The role of hormones, alternative mechanisms of cell death, the impact of central dopaminergic degeneration on behavior, and germinal layer lesions on developmental/regenerative capacity of MRL-lpr brains will also be explored. This model can provide direction for future therapeutic interventions in patients with this complex neuroimmunological syndrome.

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Section: Prelude To Cns Damage: Disruption Of the Blood-brain Barriermentioning

confidence: 99%

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Ballok

2007

Brain Research Reviews

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“…In fact, it appeared that cytokines may also modulate the secretion from the hypopituitary-hypothalamus axis and that an important neuroendocrine-immune loop exists (69,323).…”

Section: Introduction and Historical Perspectivementioning

confidence: 99%

Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

Pedersen¹,

Febbraio²

2008

Physiological Reviews

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1,637

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Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as “myokines.” Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.

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“…gp130 expression is ubiquitous, and its ability to respond differentially to each of the proteins that belong to the gp130 cytokine family is determined by the expression of the cytokines or their specific alpha receptor chains. This occurs also in the pituitary gland, where many studies have demonstrated not only the expression of gp130 mRNA (6) but also the expression of specific receptors and synthesis of gp130 cytokines in different types of pituitary cells (reviewed in [7][8][9][10], providing the cellular and molecular basis for an auto-paracrine mechanism of regulation of pituitary function. Particularly, several groups have demonstrated IL-6 production and the presence of IL-6 mRNA in anterior pituitary cells (11,12).…”

Section: Introductionmentioning

confidence: 99%

Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

Graciarena

Carbia-Nagashima²,

Onofri

et al. 2004

European Journal of Endocrinology

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Objective: gp130 cytokines are placed as auto-paracrine regulators of pituitary function, since they, as well as their receptors, have been shown to be expressed in and to act in normal and tumoral anterior pituitary cells. The objective of this work was to study their involvement in a model that shows the interaction between different cellular types that participate in a tumorigenic process. Design: The dependence of a pituitary somatotrophic cell line (MtT/S) on a gp130 cytokine-producing folliculostellate (FS) cell line (TtT/GF) for tumorigenesis in vivo has been described. In order to study the participation of gp130 cytokines in the auto-paracrine stimulation of MtT/S growth, we generated MtT/S gp130 sense (gp130-S) and gp130 antisense (gp130-AS) clones stably transfected with pcDNA3/gp130 sense and pcDNA3/gp130 antisense vectors respectively. Methods and results: Functional characterization studies revealed that gp130-AS clones have an inhibited gp130 signalling, and proliferation studies showed that they have an impaired response to gp130 cytokines but respond normally to other independent stimuli. When injected into nude mice, MtT/S clones respond differently depending on cell number; at high concentrations MtT/S clones alone generated tumours equivalent in size to tumours derived from MtT/S plus TtT/GF cells. At low concentrations, MtT/S sense and control clones generated tumours of smaller size than tumours derived from these same clones plus TtT/GF cells, showing a dependence on FS cells. In both cases MtT/S gp130-AS clones had impaired tumour development. Furthermore, vessel density was significantly lower in tumours derived from gp130-AS plus TtT/GF cells. Conclusions: This study underlines the importance of gp130 cytokines in proliferation and establishes its role in auto-paracrine pituitary growth regulation.European Journal of Endocrinology 151 595-604

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Role of the Cytokines in the Neuroendocrine-Immune System Axis

Cited by 112 publications

References 0 publications

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

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