Journal of Clinical & Experimental Pathology
Open Access

Cytokines are tiny, soluble proteins that have significant functions in immunity, inflammation, and hematopoiesis. These signaling molecules are produced by a wide variety of cells, including immune cells such as macrophages, B lymphocytes, T lymphocytes, mast cells, endothelial cells, fibroblasts, and stromal cells. Cytokines act through autocrine, paracrine, or endocrine processes, depending on the circumstances, and are essential for maintaining homeostasis and directing responses to infections, traumas, and illnesses. Cytokines are primarily grouped according to their functional roles, although there is significant overlap due to their various actions. Interleukins (IL) were once assumed to be produced and acted on primarily by leukocytes, but they now refer to a broad class of cytokines involved in immunological responses. Interleukin-1 (IL-1) to Interleukin-38 (IL-38) is currently known, with actions ranging from immune cell activation to anti-inflammatory effects. Interferons (IFNs) have an important part in antiviral defense and immune function modulation. Type I interferons have a major part in the innate immune response to viral infections, but Type II interferon is important for adaptive immunity. Tumour Necrosis Factor alpha (TNF-α) and Tumour Necrosis Factor beta (TNF-β) have important functions in systemic inflammation, including septic shock and autoimmune disorders.

Chemokines are tiny cytokines that largely control immune cell chemotaxis. Cerebrospinal Fluid (CSF) cytokines increase the formation of blood cells from hematopoietic stem cells, such as Granulocyte-Colony Stimulating Factor (G-CSF) and Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF). Cytokines attach to specific receptors on the surface of target cells, activating a range of intracellular signaling mechanisms. These pathways frequently involve Janus kinases (JAK) and Signal Transducers and Activators of Transcription (STAT) proteins, which lead to gene transcription and, ultimately, cellular responses such as proliferation, differentiation, survival, or apoptosis. Most cytokines have structural similarities, such as four alpha-helix bundles, although their roles can be extremely diverse. A single cytokine can affect several cell types depending on the presence of certain receptors and the circumstances in which it is produced. Cytokines provide an important role in both the innate and adaptive immune systems. In innate immunity, macrophages and dendritic cells rapidly generate cytokines such as IL-1, IL-6, and TNF- α in response to infections. These cytokines cause inflammation, attract immune cells to the site of infection, and stimulate local tissues to create additional cytokines and chemokines. In adaptive immunity, cytokines possess a role in T and B lymphocyte development and proliferation.

During viral infections, the cytokine response is essential for regulating viral replication. However, in severe illnesses, increased cytokine synthesis might trigger a cytokine storm. In disorders like COVID-19, high levels of cytokines such as IL-6, TNF-α, and others cause extensive inflammation, tissue destruction, and organ failure. Cytokines are now recognized as therapeutic targets due to their pivotal roles in disease. Several medications targeting cytokines or their receptors have been developed to treat autoimmune disorders, cancer, and other inflammatory conditions. TNF-α inhibitors, like infliximab and adalimumab, are commonly used to treat autoimmune illnesses such rheumatoid arthritis, Crohn's disease, and psoriasis. Tocilizumab, an antibody that inhibits the IL-6 receptor, has been licensed for the treatment of rheumatoid arthritis and is also utilized in severe COVID-19 patients to reduce the cytokine storm. Interleukin-2 (IL-2) is used as an immunotherapy in certain cancers, including metastatic melanoma and renal cell carcinoma, to improve the immune system's ability to kill cancer cells.

IFN-α is used to treat some malignancies and viral infections. Several monoclonal antibodies that target specific cytokines, such ustekinumab (which targets IL-12 and IL-23), are used to treat autoimmune illnesses such as psoriasis and Crohn's disease. The involvement of cytokines in disease remains an important field of investigation. The development of cytokine tests and the capacity to characterize cytokine levels in patients has allowed clinicians to gain a better understanding of disease causes, forecast outcomes, and adjust medications. For example, monitoring cytokine levels in patients with sepsis or COVID-19 may help in identifying those at risk of severe disease and guiding therapeutic decisions. Cytokines have critical roles in immune system regulation and inflammation. Their functions are many, ranging from stimulating immunological responses to infections to maintaining tissue homeostasis and controlling the repair process. When cytokines are dysregulated, they can contribute to the development of a variety of diseases, including autoimmune disorders, infectious diseases, malignancies, and metabolic problems. As a result, cytokine-based therapies have become known as an essential element in the treatment of many different inflammatory and immune-mediated disorders. Continued study into cytokine biology is anticipated to generate new treatment techniques for managing a wide range of disorders.