Pdf on cytokines

In addition to hematogenous macrophage infiltration, the satellite glia that surround the somata of sensory neurons proliferate [ 44 ], elaborate processes [ 45 ], and become immunoreactive for glial fibrillary acidic protein GFAP [ 46 ]. There is evidence that pro-inflammatory cytokines e. Results obtained from IL-6 knockout mice indicates that IL-6 plays a facilitating role in sympathetic sprouting induced by nerve injury and that its effect on pain behavior is indirectly mediated through sympathetic sprouting in the DRG [ 18 ].

Most recently, it is reported that localized inflammation of the DRG up-regulates a number of pro-inflammatory cytokines including IL-6 and induces abnormal sympathetic sprouting in the absence of peripheral nerve injury [ 2 ]. It suggests a possible correlation between inflammatory responses and sympathetic sprouting, which are two well-known mechanisms implicated in various chronic pain states.

In summary, proinflammatory cytokines are involved in the development of inflammatory and neuropathic pain. These specific cytokines or antagonists would act to disrupt the hyperexcitability cycle taking place in the sensory neurons, providing a new, non-opioid therapeutic approach for the treatment of pathological pain due to inflammation or peripheral nerve injury.

National Center for Biotechnology Information , U. Int Anesthesiol Clin. Author manuscript; available in PMC Nov Author information Copyright and License information Disclaimer. Copyright notice. The publisher's final edited version of this article is available at Int Anesthesiol Clin. See other articles in PMC that cite the published article. Abstract Cytokines are small secreted proteins released by cells have a specific effect on the interactions and communications between cells.

Keywords: cytokine, inflammation, pain, hyperalgesia. Introduction Inflammatory responses in the peripheral and central nervous systems play key roles in the development and persistence of many pathological pain states [ 1 ].

Open in a separate window. Figure 1. Cytokines and pain Pro-inflammatory cytokines Proinflammatory cytokines are produced predominantly by activated macrophages and are involved in the up-regulation of inflammatory reactions. Chemokines A variety of cytokines are known to induce chemotaxis. Anti-inflammatory cytokines The anti-inflammatory cytokines are a series of immunoregulatory molecules that control the pro-inflammatory cytokine response. Glial activation in CNS and PNS In the CNS, there are two types of glial cells, microglia and astrocytes, which can be activated by excitatory neurotransmitters released from nearby neurons.

Mechanisms underlying cytokines-mediated pathological pain There is evidence that pro-inflammatory cytokines e. References 1. Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain. Adv Exp Med Biol. Robust increase of cutaneous sensitivity, cytokine production and sympathetic sprouting in rats with localized inflammatory irritation of the spinal ganglia.

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Mediation through increased prostaglandin E2 levels. Interleukin-1 mediates the behavioral hyperalgesia produced by lithium chloride and endotoxin. Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain.

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Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor alpha. Br J Pharmacol. The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Cytokines and peripheral nerve disorders. Eur Cytokine Netw. Wagner R, Myers RR. Endoneurial injection of TNF-alpha produces neuropathic pain behaviors.

Intrathecal interleukin-1 receptor antagonist and tumor necrosis factor binding protein exhibit an antiallodynic effect in a rat model of neuropathic pain.

Soc Neurosci Abstr. Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion.

Localization of monocyte chemoattractant peptide-1 expression in the central nervous system in experimental autoimmune encephalomyelitis and trauma in the rat. J Immunol. Taskinen HS, Roytta M. J Peripher Nerv Syst. Chemokines and glycoprotein produce pain hypersensitivity by directly exciting primary nociceptive neurons.

Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Glial activation and pathological pain. Neurochem Int. Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin Mol Pain. Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum. Transforming growth factor beta isoforms in the adult rat central and peripheral nervous system.

Physiological actions and clinical applications of transforming growth factor-beta TGF-beta Growth Factors. Interleukin-6 and transforming growth factor-beta 1 mRNAs are induced in rat facial nucleus following motoneuron axotomy.

Eur J Neurosci. Macrophage deactivating factor and transforming growth factors-beta 1 -beta 2 and -beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma. Nitric oxide NO and nociceptive processing in the spinal cord. Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. Nerve injury proximal or distal to the DRG induces similar spinal glial activation and selective cytokine expression but differential behavioral responses to pharmacologic treatment.

J Comp Neurol. Cytokines are a large, diverse family of small proteins or glycoproteins usually smaller than 30 kDa. Although initially described for their immunomodulatory capabilities, additional roles separate from the immune system in developmental processes are also documented, such as cell differentiation and directed migration.

Influencing both innate and adaptive immune responses, the two principal producers of cytokines are helper T cells Th cells and macrophages , although they can be transiently induced and secreted by virtually all nucleated cells. The downstream effects of a particular cytokine occurs through its high-affinity binding of its receptor expressed on the surface of a target cell.

This action may occur in an autocrine acts on same cell , paracrine acts on nearby cell or endocrine acts on distant cell; not the normal manner for cytokine responses manner. Receptor engagement triggers intracellular signalling cascades leading to altered gene expression in the target cell, which lead to a biological effect Figure 1.

Differentiation, proliferation and activation of the target cell are all effects which can be detected after cytokine stimulation. The multiple cytokines detected in the extracellular milieu at any given time during an immunological response can interact in pleiotropic different effects on different types of target cells , redundant multiple cytokines have same effect , synergic cooperative effect of multiple cytokines , antagonistic inhibition of one cytokines effects by another and cascade induction multiple-step feed-forward mechanism for the amplified production of a particular cytokine manners.

These interactions make it possible for the coordinated recruitment and activation of an entire network of immune cells by a relatively small number of cytokines produced by a single cell type e. In healthy individuals, cytokine action is regulated by their transient production only in response to either antigen or potent inflammatory stimuli, the short half-life of cytokines in extracellular fluids and compartments, and the restricted receptor expression profiles on the surface of both activated and unactivated target cells, as well as other mechanisms.

Of course, there are examples of cytokine dysregulation which result in pathological disease. Colony stimulating factors CSF are part of the haematopoietin family of cytokines. CXCL10 induces the migration of Th1 cells from areas of low CXCL10 concentrations towards areas with high concentrations of the molecule, such as the site of an infection and inflammation Figure 3. Register Log in.