The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions.

Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes in the body. Its wide-ranging functions underscore its importance in maintaining health. Dysregulated IL-6 is closely associated with many diseases, making it a key research and therapeutic target. Elevated IL-6 levels in the central nervous system worsen neuroinflammation in neurodegenerative diseases by activating microglia and astrocytes and releasing pro-inflammatory cytokines and neurotoxic molecules. Moreover, dysregulated IL-6 weakens the blood-brain barrier, exacerbating neuroinflammation and neuronal damage by allowing peripheral immune cells and inflammatory mediators to enter the brain. Mesenchymal stem cells (MSCs) show promise in modulating neuroinflammation by regulating IL-6 levels. They effectively suppress pro-inflammatory cytokines, including IL-6, while promoting anti-inflammatory factors. This therapeutic approach highlights the importance of targeting IL-6 and other inflammatory mediators to alleviate neuroinflammation and its adverse effects on neurological disorders. This review provides a comprehensive overview of IL-6's involvement in neurological disorders, examining endogenous IL-6 and IL-6 derived from MSCs. We explore IL-6's mechanisms affecting neuronal function, survival, and immune modulation in the central nervous system. Additionally, we discuss the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. By elucidating IL-6's interplay with neurological pathologies, this review offers insights into novel therapeutic strategies targeting IL-6 signaling pathways for neurological disorders.

Photobiomodulation Improves the Inflammatory Response and Intracellular Signaling Proteins Linked to Vascular Function and Cell Survival in the Brain of Aged Rats.

Photobiomodulation is a non-pharmacological tool widely used to reduce inflammation in many tissues. However, little is known about its effects on the inflammatory response in the aged brain. We conducted the study to examine anti-inflammatory effects of photobiomodulation in aging brains. We used aged rats (20 months old) with control (handled, laser off) or transcranial laser (660 nm wavelength, 100 mW power) treatments for 10 consecutive days and evaluated the level of inflammatory cytokines and chemokines, and the expression and activation of intracellular signaling proteins in the cerebral cortex and the hippocampus. Inflammatory analysis showed that aged rats submitted to transcranial laser treatment had increased levels of IL-1alpha and decreased levels of IL-5 in the cerebral cortex. In the hippocampus, the laser treatment increased the levels of IL-1alpha and decreased levels of IL-5, IL-18, and fractalkine. Regarding the intracellular signaling proteins, a reduction in the ERK and p38 expression and an increase in the STAT3 and ERK activation were observed in the cerebral cortex of aged rats from the laser group. In addition, the laser treatment increased the hippocampal expression of p70S6K, STAT3, and p38 of aged rats. Taken together, our data indicate that transcranial photobiomodulation can improve the inflammatory response and the activation of intracellular signaling proteins linked to vascular function and cell survival in the aged brain.

Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease.

The concept of central nervous system (CNS) inflammation has evolved over the last decades. Neuroinflammation is the response of reactive CNS components to altered homeostasis, regardless of the cause to be endogenous or exogenous. Neurological diseases, whether traumatic, neoplastic, ischemic, metabolic, toxic, infectious, autoimmune, developmental, or degenerative, involve direct and indirect immune-related neuroinflammation. Brain infiltrates of the innate and adaptive immune system cells appear in response to an infective or otherwise noxious agent and produce inflammatory mediators. Mediators of inflammation include local and recruited cells and signals. Processes derived from extrinsic and intrinsic CNS diseases also elicit the CNS inflammatory response. A deeper understanding of immune-related inflammation in health and disease is necessary to find potential therapeutic targets for preventing or reducing CNS damage. This review is aimed at discussing the innate and adaptive immune system functions and their roles in regulating brain cell responses in disease and homeostasis maintenance.