The cytokines or cytokines are soluble signaling proteins or glycoproteins produced by various types of cells in the body, especially by cells of the immune system such as leukocytes: neutrophils, monocytes, macrophages, and lymphocytes (B cells and T cells).
Unlike other specific receptor binding factors that trigger long and complex signaling cascades that often involve protein kinase sequences (the cyclic AMP pathway, for example), cytokines exert more direct effects..
These soluble factors bind to receptors that directly activate proteins that have direct functions in gene transcription, since they are capable of entering the nucleus and stimulating the transcription of a specific set of genes..
The first cytokines were discovered more than 60 years ago. However, the molecular characterization of many of them was quite later. Neural growth factor, interferon, and interleukin 1 (IL-1) were the first cytokines described.
The name "cytokine" is a general term, but in the literature distinctions are made regarding the cell that produces them. Thus, there are lymphokines (produced by lymphocytes), monokines (produced by monocytes), interleukins (produced by a leukocyte and acting on other leukocytes), etc..
They are especially abundant in vertebrate animals, but their existence has been determined in some invertebrates. In the body of a mammal, for example, they can have additive, synergistic, antagonistic functions or they can even activate each other..
They can have autocrine action, that is, they act on the same cell that produces them; or paracrine, which means that they are produced by one type of cells and act on others around them.
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All cytokines are "pleiotropic", that is, they have more than one function in more than one type of cell. This is because the receptors that respond to these proteins are expressed in many different types of cells..
It has been determined that there is some functional redundancy between many of them, since several types of cytokines can have convergent biological effects, and it has been suggested that this is related to the sequence similarities in their receptors.
Like many messengers in cell signaling processes, cytokines have powerful actions at very low concentrations, so low that they can be in the nanomolar and femtomolar range thanks to the fact that their receptors are extremely related to them..
Some cytokines work as part of a "cascade" of cytokines. That is, it is common for them to act in synergy and their regulation often depends on other inhibitory cytokines and additional regulatory factors..
Some cytokines come from genes of constitutive expression since, for example, it is necessary to maintain constant hematopoietic levels.
Some of these proteins with constitutive expression are erythropoietin, interleukin 6 (IL-6) and certain factors that stimulate the growth of cell colonies that contribute to the differentiation of many white cells.
Other cytokines are pre-synthesized and stored as cytosolic granules, membrane proteins, or complexed with binding proteins to the cell surface or to the extracellular matrix..
Many molecular stimuli positively regulate the expression of genes that code for cytokines. There are some of these molecules that increase the gene expression of other cytokines, and there are also many that have inhibitory functions that limit the action of other cytokines..
The function of cytokines is also controlled by the processing of the precursor forms of these proteins. Many of them are initially produced as active integral membrane proteins that require proteolytic cleavage to become soluble factors..
Example of cytokines under this type of production control are the epidermal growth factor EGF (from the English “ANDpidermal Growth Factor"), the tumor growth factor TGF (from the English "Tumoral Growth Factor"), interleukin 1β (IL-1β) and tumor necrosis factor TNFα (from the English “Tumor Necrosis Factor").
Other cytokines are secreted as inactive precursors that must be enzymatically processed to be activated and some of the enzymes responsible for this processing of certain cytokines involve proteins of the cysteine protease caspase family..
Cytokines can have highly variable weights, so much so that the range has been defined between around 6 kDa and 70 kDa..
These proteins have highly variable structures, being able to be made up of barrels of alpha helices, complex structures of parallel or antiparallel β-folded sheets, etc..
There are several types of families of cytokines and the number continues to grow in view of the great diversity of proteins with functions and characteristics similar to them that are discovered every day in the scientific world..
Its nomenclature is far from any systematic relationship, since its identification has been based on different parameters: its origin, the initial bioassay that defined it and its functions, among others..
The current consensus for the classification of cytokines is essentially based on the structure of their receptor proteins, which are contained in a small number of families with highly conserved characteristics. Thus, there are six families of cytokine receptors that are grouped according to the similarities in the sequence of their cytosolic portions:
Receptors for cytokines can be soluble or membrane bound. Soluble receptors can regulate the activity of these proteins by acting as agonists or antagonists in the signaling process..
Many cytokines employ soluble receptors, including various types of interleukins (IL), neural growth factors (NGF), tumor growth factors (TGF), and others..
It is important to remember that cytokines function as chemical messengers between cells, but not exactly as molecular effectors, since they are necessary to activate or inhibit the function of specific effectors..
One of the "unifying" functional characteristics among cytokines is their participation in the body's defense, which is summarized as "the regulation of the immune system", which is particularly important for mammals and many other animals..
They participate in the control of hematopoietic development, in intercellular communication processes and in the body's responses against infectious agents and inflammatory stimuli.
Since they are normally found in low concentrations, the quantification of the concentration of cytokines in tissues or body fluids is used as a biomarker for the prediction of disease progress and the monitoring of the effects of drugs administered to patients. sick patients.
In general, they are used as markers of inflammatory diseases, including implant rejections, Alzheimer's, asthma, arteriosclerosis, colon cancer and other cancers in general, depression, some heart and viral diseases, Parkinson's, sepsis, liver damage, etc..
Most of the cytokines are secreted by cells. Others can be expressed in the plasma membrane and there are some that remain in what could be considered as a “reserve” in the space comprised by the extracellular matrix..
Cytokines, as mentioned, have effects in vivo that depend on the environment where they are. Its action occurs through signaling cascades and interaction networks that involve other cytokines and other factors of different chemical nature..
They usually participate in the interaction with a receptor that has a target protein that is activated or inhibited after its association, which has the ability to act directly or indirectly as a transcriptional factor on particular genes..
Also known as lymphocyte activating factor (LAF), endogenous pyrogen (EP), endogenous leukocyte mediator (LEM), catabolin, or mononuclear cell factor (MCF).
It has many biological functions on many cell types, notably B, T cells, and monocytes. It induces hypotension, fever, weight loss, and other responses. It is secreted by monocytes, tissue macrophages, Langerhans cells, dendritic cells, lymphoid cells, and many others..
It has other names such as mast cell growth factor (MCGF), multiple colony stimulating factor (multi-CSF), hematopoietic cell growth factor (HCGF), and others..
It has important functions in stimulating the colony formation of erythrocytes, megakaryocytes, neutrophils, eosinophils, basophils, mast cells and other cells of monocytic lineages..
It is synthesized mainly by activated T cells, mast cells and eosinophils.
It is derived from plasminogen and is an angiogenesis inhibitory cytokine, which gives it functions as a potent blocker of neovascularization and the growth of tumor metastases in vivo. It is generated by the proteolytic cleavage of plasminogen mediated by the presence of cancers.
It acts by stimulating the growth of epithelial cells, accelerates the emergence of teeth and the opening of the eyes in mice. In addition, it works in inhibiting gastric acid secretion and is involved in wound healing..
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