Cytokines

Definitions & Key takeaways

Cytokines are cell signaling proteins that play an essential role in the regulation of immune responses, including inflammation and cell growth. There are many different cytokines, and they can be classified into five main classes. They include Interleukins, Tumor Necrosis Factors, Interferons, Transforming Growth Factors, and colony-stimulating factors.

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Cytokines are tiny proteins that are secreted by both immune and non immune cells to communicate with one another. Cytokines bind to receptors and trigger a response in the receiving cell.
Oftentimes cytokines promote activation, proliferation and differentiation of immune cells. But they can do other things like help increase the body temperature causing a fever.
Now, cytokines signal to other cells mainly through autocrine and paracrine signaling. But to a lesser extent, endocrine signaling can also be employed.
Now, autocrine means the cell producing the cytokine is also the cell responding to the cytokine. An example is interleukin two or IL two, which is secreted by CD four positive T helper cells.
Interleukin two promotes the proliferation of T lymphocytes including the CD four positive T helper cell that produced it.
Paracrine means that the cytokine is produced by one cell and that it affects cells in the near vicinity. Once again, an example is interleukin two because it helps nearby CD eight positive cytotoxic T cells proliferate.
That's important because the CD eight positive cytotoxic T cells aren't good at making their own interleukin two. Finally, there's endocrine which is when the cytokine affects a cell that's far away perhaps in a different organ.
An example would be the inflammatory triad of interleukin one beta or il one beta interleukin six or il six and tumor necrosis factor alpha or TNF alpha.
These cytokines are produced by macrophages and dendritic cells. During acute inflammation, these cytokines travel to the liver and brain in response, the liver produces acute phase reactants like c reactive protein and mannose binding lectin.
And the brain increases the body's temperature, triggering a fever. At the same time, interleukin one beta and tumor necrosis factor alpha also help to recruit other immune cells to the site of injury, enhancing the inflammatory response.
Overall, there are five main classes of cytokines. The first and most varied group are the interleukins which are numbered in the order they were identified.
So the numbers actually don't tell us anything about what they do. It used to be thought that interleukins were only sent between leukocytes or white blood cells, but it turns out that they're released and act on both leukocytes as well as non leukocytes.
The second group are the tumor necrosis factors or TNFs. Tnfs are named because they were discovered by their ability to kill tumor cells.
Now known to be because they elicit inflammation and the inflammatory cells, neutrophils and macrophages actually do the killing tumor necrosis factor alpha, tumor necrosis factor beta, also called lymphotoxin alpha or LT alpha.
And the lymphotoxin beta or LT beta are known to have a wide variety of biological effects in the inflammatory response including activating endothelial cells to up regulate expression of adhesion molecules and increasing their vascular permeability.
The third group are the interferons and as their name implies, they interfere with processes like viral replication. There are two types of interferons, type one and type two type one.
Interferons include interferon alpha and interferon beta. And they're usually produced by virally infected cells and some dendritic cells responding to the viral infection in order to limit viral replication.
Now, the only type two interferon is interferon gamma. This molecule is the most powerful macrophage activator.
And it also activates CD four positive helper T cells which then secrete their own interferon gamma and interleukin two.
The fourth group includes the colony stimulating factors. These cytokines bind to surface receptors on hematopoietic stem cells causing them to proliferate and differentiate.
Some examples include granulocyte macrophage colony stimulating factor or GMCSF, which is a cytokine secreted by a wide variety of immune and non immune cells that stimulates the development of granulocytes and macrophages.
The fifth and final group includes the transforming growth factors. There are more than 30 different TG FS and the most important in the immune system is TGF beta, TGF beta is an inhibitory factor that suppresses proliferation and differentiation of various cells.
It also helps CD four positive T cells to develop into a regulatory cell that can slow down or stop the overall immune response.
You can think of transforming growth factor beta as helping to put on the brakes. So broadly speaking, there are 100s of cytokines.
Some are pro inflammatory, some are anti inflammatory and regulate the immune response and some are growth factors. It's kind of like cooking where each cytokine is like an ingredient.
One meal might call for onions, garlic, asparagus, mushrooms and rice. Whereas another meal might call for garlic, tomatoes and pasta.
Ultimately in response to an event like damage or infection, we're combining different cytokines to get the desired immune response.
And that's why you'll see one cytokine included in different pathways. Each one resulting in a different immune response.
The highly proinflammatory response for fighting intracellular pathogens include cytokines that enhance the innate or adaptive immune response.
These include interferon alpha and interferon beta, which are produced by virally infected cells and work on various immune cells to help interfere with viral replication.
In addition, there's interleukin one beta tumor necrosis factor alpha and interleukin six, which are produced by macrophages and dendritic cells.
Interleukin six can additionally be produced by T and B cells. Their major targets are various immune cells as well as endothelial cells where they promote migration of leukocytes and the liver and brain where they cause production of acute phase reactants and cause fever as time passes, the immune system moves into the adaptive immune response.
And cytokines are what help CD four positive helper cells differentiate into specialized subsets called th one th two or th 17 cells going one by one interleukin two is produced by CD four positive helper cells.
And it also acts on CD four positive helper cells as well as on CD eight positive cytotoxic T cells and B cells interleukin 12 is produced largely by dendritic cells in macrophages and it activates natural killer cells.
Interleukin 12 also helps CD four positive T cells differentiate into CD four positive th one cells which produce interferon gamma and lymphotoxin.
On the other hand, the cytokines interleukin six, interleukin 23 and transforming growth factor beta helps CD four positive T cells differentiate into CD four positive th 17 cells which produce interleukin.
17 interleukin 17 is a cytokine that helps recruit neutrophils to the site of inflammation. This collection of cytokines are effective against viruses, bacteria and some cancers.
The inflammatory response that's geared toward parasitic infections is created using interleukin four, interleukin five and interleukin 13.
These cytokines help the immune system handle large unwieldy parasites and also induce asthma and allergy responses. They induce T cells to differentiate into th two helper T cells and stimulate mast cells, basophils and eosinophils.
The th two cells secrete even more of these cytokines which perpetuates the response. The regulatory immune response is immunosuppressive.
In this case, we use one cytokine from an inflammatory response in your leukin 10, along with transforming growth factor beta.
The overall effect is to inhibit the inflammatory response by getting T cells to develop into regulatory T cells. Regulatory T cells produce more interleukin 10 and transforming growth factor beta.
And that perpetuates the anti inflammatory state. The key is that interleukin 10 and transforming growth factor beta make nearby cells reduce their expression of co stimulatory receptors.
And ultimately, that inhibits immune cell growth. The fourth type of cytokine response is a little different from the other immune responses because its main goal is to replenish the immune cells.
Growth factors like GMCSF M CSF and interleukin seven are produced by bone marrow stromal cells where they get bone marrow progenitor cells to differentiate GMCSF and M CSF promote the differentiation of monocytes and granulocytes.
While interleukin seven promotes the differentiation of progenitor cells into lymphocytes like B cells, T cells and natural killer cells.
The last type of cytokine response is also a process that happens constantly. These are the air traffic controllers of the cytokine world and they tell everyone where to go.
The group of cytokines are called chemokines. And these are chemotactic agents meaning that they help cells move toward the site of inflammation.
One such chemokine is interleukin eight which is generated by fibroblasts, neutrophils and macrophages to recruit phagocytes to the site of inflammation.
Finally, a potent inductor of chemokine production is interleukin 17, which is generated by CD four positive th 17 cells during inflammation.
All right, as a quick recap cytokines help facilitate communication mainly through autocrine and paracrine signaling but also through endocrine signaling there are five main classes, interleukins, tumor necrosis factors, interferons, transforming growth factors and colony stimulating factors and they can be mixed to create different functional responses.
The main response types are the acute inflammatory proinflammatory parasite slash allergy, regulatory growth and differentiation and chemotactic agents.