Interleukin 1 beta (IL-1β) is a cytokine involved in pro-inflammatory responses. It is produced by activated macrophages, natural killer cells, monocytes, and neutrophils in response to wounds, infections, or microbial endotoxins and is processed to its active state by caspase 1. It mediates inflammatory responses and plays a role in cell proliferation, apoptosis, and differentiation. IL-1β inflammation within the central nervous system is known to result in pain and hypersensitivity. High levels of IL-1β are associated with autoinflammatory diseases, particularly the group of rare heterozygous dominant diseases known as cryopyrin-associated periodic syndromes, that often affect the skin, joints, eyes, and nervous system. Inhibition of IL-1β treats these diseases and eases symptoms in common conditions such as type 2 diabetes, cardiac failure, gout, and rheumatoid arthritis. Dysregulated IL-1β is associated with tumor formation in a wide variety of cancers.
Interleuken 6 (IL-6) has the capability to behave as both a pro-inflammatory cytokine and an anti-inflammation myokine. As a cytokine, it is secreted by macrophages in response to microbial activity, to regulate the progression of fever through raising the temperature of muscle and fat, as well as crossing the blood-brain barrier to alter the body’s temperature set point in the hypothalamus. It acts through T cells and macrophages fighting infection and causing inflammation. As a myokine, it is released by contracting muscles during exercise, and inhibits the activity of pro-inflammatory agent TNF-alpha, reducing system-wide inflammation. In addition to its functions in the immune system, IL-6 aids in bone remodeling and maintenance by stimulating the production of osteoclasts. Clinically, IL-6 is implicated in the inflammatory and autoimmune symptoms of many diseases, including diabetes, asthma, atherosclerosis, depression, Alzheimer’s disease, rheumatoid arthritis, and many cancers. High levels of IL-6 are common in advanced cancer patients and are correlated with low survival rates. IL-6 has the ability to induce epigenetic modifications of gene transcription in the brain, and these IL-6 modifications are associated with schizophrenia and major depressive disorder.
Tumor necrosis factor alpha (TNFα) is a prototypic ligand of the TNF superfamily. It is a versatile cytokine that plays a central role in inflammation, immune system development, apoptosis, and lipid metabolism. TNFα is an important endogenous pyrogen, its release quickly induces fever. It also causes apoptotic cell death, cachexia, inflammation, and has the ability to inhibit tumorigenesis and viral replication. It is chemoattractive to many immune cells, particularly neutrophils. Cell surface TNFα can induce the lysis of neighboring tumor cells and virus infected cells and has the ability to generate its own downstream cell signaling. It is produced chiefly by activated macrophages, although it is produced in low levels by a wide variety of immune, epithelial, endothelial, and tumor cells such as CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, and neurons. TNFα also plays an important role in metabolism, with the ability to induce insulin resistance and regulate appetite through interactions with the hypothalamus. Dysregulation of TNF production has been implicated in a variety of human diseases including Alzheimer’s disease, inflammatory bowel disease, arthritis, cancer, and psoriasis.
Interferon gamma (IFNγ), also known as Type II interferon, is a cytokine that plays a critical role in the innate and adaptive immune systems. It serves as protection against viral infections, as well as some bacterial and protozoal infections, and plays a role in tumor control. It is capable of inhibiting viral replication and works to modulate immunological responses to multiple kinds of pathogens, with effects including promoting natural killer cell activity, activating macrophages to destroy foreign cells, increasing antigen presentation, and inducing the expression of numerous immune defense factors. IFNγ is primarily produced by natural killer and natural killer T cells during the innate immune response and by CD4 and CD8 cytotoxic T lymphocyte effector T cells as part of an adaptive response. It has been shown to halt growth and induce apoptosis in some types of tumors. During pregnancy, IFNγ aids in the remodeling of the uterine wall and placenta to accommodate a zygote.
Interleuken 1 alpha (IL-1α), also known as hematopoietin 1, is a cytokine that plays a role in inflammation, fever, and sepsis. It is produced by macrophages, neutrophils, and endothelial and epithelial cells. In the skin, IL-1α is regularly produced at high levels and helps maintain skin barrier function against pathogens as well as overall skin condition. As part of the immune response, its production is by microbial exposure. It is responsible for releasing inflammatory mediators and acute phase proteins. The severity of inflammation, fever, and sepsis are associated with circulating IL-1α levels. IL-1α inhibitors are a potential target for therapeutics to treat and prevent these conditions as well as mediate skin conditions such as acne. Additionally, IL-1a is part of the pathway that activates tumor necrosis factor-alpha and helps kill some kinds of cancer cells. It also supports stem cell expansion and osteoclast formation following bone marrow transplant.
Interleukin 10 (IL-10) is a class-2 anti-inflammatory cytokine, also known as human cytokine synthesis inhibitory factor (CSIF). It impacts many areas of immunoregulation and inflammation, with numerous pleiotropic effects in the immune system. As an anti-inflammatory, it downregulates MHC class II expression, inhibits the synthesis and activity of many inflammatory cytokines, and reduces co-stimulatory factors on macrophages. It also enhances the release of other anti-inflammatory mediators by monocytes and macrophage, particularly during exercise. It enhances B cell proliferation, differentiation, survival, and antibody production. IL-10 has anti-tumor effects, reducing tumor growth and decreasing metastatic burden in the body. IL-10 deficiency is associated with chronic inflammatory and autoimmune diseases, including multiple sclerosis, Crohn’s disease, inflammatory bowel disease, psoriasis, and rheumatoid arthritis. IL-10 is currently under investigation as a potential therapeutic for many conditions, including cancer treatments and reducing symptoms in inflammatory disorders.
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