Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain

Abstract

Cytokines and chemokines are proteins that coordinate the immune response throughout the body. The dysregulation of cytokines and chemokines is a central feature in the development of neuroinflammation, neurodegeneration, and demyelination both in the central and peripheral nervous systems and in conditions of neuropathic pain. Pathological states within the nervous system can lead to activation of microglia. The latter may mediate neuronal and glial cell injury and death through production of proinflammatory factors such as cytokines and chemokines. These then help to mobilize the adaptive immune response. Although inflammation may induce beneficial effects such as pathogen clearance and phagocytosis of apoptotic cells, uncontrolled inflammation can result in detrimental outcomes via the production of neurotoxic factors that exacerbate neurodegenerative pathology. In states of prolonged inflammation, continual activation and recruitment of effector cells can establish a feedback loop that perpetuates inflammation and ultimately results in neuronal injury. A critical balance between repair and proinflammatory factors determines the outcome of a neurodegenerative process. This review will focus on how cytokines and chemokines affect neuroinflammation and disease pathogenesis in bacterial meningitis and brain abscesses, Lyme neuroborreliosis, human immunodeficiency virus encephalitis, and neuropathic pain.

Tumor Necrosis Factor Alpha-Induced Recruitment of Inflammatory Mononuclear Cells Leads to Inflammation and Altered Brain Development in Murine Cytomegalovirus-Infected Newborn Mice

“…The microglial subset expressed IP10, consistent with the function of activated microglia in the recruitment of effector leukocytes (Fig. 10A) (80). In contrast, IFN-␥ expression was not detected in the microglial subset, and the level of expression of IFN-␥ in nc-Mo was modest in comparison to the level of expression detected in lymphocytes present in the brain (Fig.…”

Parkinson’s disease and enhanced inflammatory response

“…26 Activated microglia also produce pro-inflammatory cytokines which can cause neurotoxicity as well as chemokines that recruit leukocytes to the CNS exacerbating inflammatory response. 27 Transient activation is necessary for local tissue repair while sustained activation of microglia can lead to neurodegenerative pathology. It has been proposed that a self-perpetuating cycle of microglial activation results from discharge of chemoattractants by DA neurons undergoing death leading to further activation of microglia and neuroinflammation.…”

Physiology and Pathology of Neuroimmunology: Role of Inflammation in Parkinson’s Disease

“…An increase in total iron concentration in the substantia nigra has been reported in PD, although the underlying mechanism is not understood [49]. Accelerated α-synuclein aggregation in turn may induce the formation of more ROS, and when the dopaminergic neurons are within an oxidative environment, the α-synuclein accumulation is increased, thereby generating a vicious cycle that leads to neuronal death [50,51]. Inflammation is a complex cascade of physiological responses to a harmful stimulus from the environment, and the CNS has a specialized immunity through the action of glial cells.…”