Cytokine
Cytokines are small proteins or peptides that act as cell-signaling molecules in the immune system and other biological processes. They play a crucial role in mediating communication between various cells, including immune cells, and are involved in regulating immune responses, inflammation, hematopoiesis (the formation of blood cells), and numerous other physiological and pathological processes.
Cytokines and angiogenic factors are closely linked to the brain cancer behavior. Moreover, recent studies suggest a link between inflammation and tumorigenesis, underlying the complex nature of this topic, especially the anti- and pro-tumoral activities of inflammation and the two-way interactions between immune and tumor cells. The current understanding of the mechanisms by which CNS cancer cells modulate the immune system, especially how bi-directional communications between immune cells and tumor cells create an immunosuppressed microenvironment, gives important information about the promotion of tumor survival and growth 1).
Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide.
Functions
Cell Signaling: Cytokines are released by immune cells and other cell types in response to various stimuli, such as infections or tissue damage. They serve as signaling molecules that transmit information between cells.
Immunomodulation: Cytokines help regulate the immune system by influencing the activation, differentiation, and function of immune cells, such as T cells, B cells, macrophages, and natural killer (NK) cells.
Inflammation: Many cytokines are involved in the initiation and regulation of inflammatory responses. Proinflammatory cytokines, for example, promote inflammation, while anti-inflammatory cytokines help resolve inflammation.
Cell Recruitment: Some cytokines, known as chemokines, guide immune cells to specific sites within the body where they are needed, such as infection or injury sites.
Hematopoiesis: Cytokines participate in the regulation of blood cell development and maturation, influencing processes like erythropoiesis (production of red blood cells) and leukopoiesis (production of white blood cells).
Antiviral Defense: Certain cytokines, like interferons, play a critical role in antiviral defense by inhibiting viral replication and boosting the immune response against viruses.
Tissue Repair: Cytokines can also contribute to tissue repair and regeneration following injury or infection.
Classification
Cytokines can be classified into several different categories based on their functions and structural characteristics. Here are some common classifications of cytokines:
Based on Function:
Proinflammatory Cytokines: These cytokines promote inflammation and immune responses. Examples include Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α). Anti-Inflammatory Cytokines: These cytokines dampen inflammatory responses and help regulate immune reactions. Examples include Interleukin-10 (IL-10) and Transforming Growth Factor-beta (TGF-β). Chemokines: Chemokines are involved in guiding immune cells to sites of infection or tissue damage. They play a role in cell migration and recruitment. Examples include CCL2 (MCP-1), CXCL8 (IL-8), and CCL5 (RANTES). Interferons: Interferons are involved in antiviral responses and immune regulation. Examples include Interferon-alpha (IFN-α) and Interferon-gamma (IFN-γ). Interleukins: Interleukins are a diverse group of cytokines that regulate various immune functions. They are numbered (e.g., IL-2, IL-4, IL-12) based on the order of their discovery. Based on Cellular Source:
Monokines: Cytokines produced primarily by monocytes and macrophages. Lymphokines: Cytokines produced primarily by lymphocytes, such as T cells and B cells. Based on Structural Characteristics:
Type I Cytokine Receptors: These cytokines bind to receptors that have a common γ (gamma) chain. Examples include IL-2, IL-4, and IL-7. Type II Cytokine Receptors: These cytokines bind to receptors that do not have a common γ chain. Examples include IFN-γ and IL-10. Chemokine Receptors: Chemokines bind to specific G protein-coupled receptors (GPCRs) on target cells. Based on Biological Effects:
Hematopoietic Cytokines: Cytokines that regulate the development and function of blood cells, such as erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF). Th1 Cytokines and Th2 Cytokines: These classifications are based on the types of T-helper (Th) cell responses they promote. Th1 cytokines (e.g., IFN-γ) are associated with cell-mediated immune responses, while Th2 cytokines (e.g., IL-4) are associated with antibody-mediated immune responses. It's important to note that cytokines often have pleiotropic effects, meaning they can have multiple functions and can act in a complex network of interactions within the immune system. Additionally, the classification of cytokines continues to evolve as our understanding of these molecules deepens through ongoing research.
Cytokines include chemokines, interferons, interleukins, lymphokines, tumor necrosis factor but generally not hormones or growth factors. Cytokines are produced by broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell.
Several factors account for the tumorigenicity of human gliomas, including cytokines and their receptors.
see Interleukins
Inflammatory cytokines, such as interleukin 6 and tumor necrosis factor-α, are gaining attention as important etiologic factors associated with discogenic pain.
Inflammasomes are multiprotein complexes that trigger the activation of caspase 1 and subsequently the maturation of proinflammatory cytokines interleukin-1β and interleukin-18. These cytokines play a critical role in mediating inflammation and innate immunity response. Among various inflammasome complexes, the NLRP3 inflammasome is the best characterized, which has been demonstrated as a crucial role in various diseases.