Cells and Cytokines

This section aims to provide readers with a basic understanding of the biological processes that cause arthrofibrosis. We have tried to keep this explanation as simple as possible, however, the body is an amazing and highly complex system making oversimplification a significant risk. Because this is well established science this page has a different format. For references or more information please see Wikipedia.

Arthrofibrosis is caused by cell biology

Everything that happens inside our bodies, other than accidents and surgery, is the result of cell biology. It is our cellular processes that heal wounds, create scar tissue and unfortunately, in some cases, creates fibrosis. So, although arthrofibrosis may be initiated by injury or surgery, to understand it we need to understand the processes at work in the body.

Cells

Cells are the basic unit of all living things. In a human there are as many as 30 trillion cells as well as many microorganisms, predominantly bacteria and fungi, and all are important for the way that we function. Microorganisms such as bacteria are single cells. They “talk” to each other and to us with proteins they secrete and can behave cooperatively or in competition. Bacteria are essential for the human digestive system, as well as for the functioning of our hormones and immune system. For more information about the construction of cells see Wikipedia https://en.wikipedia.org/wiki/Cell_(biology)

Humans are multicellular hence each individual consists of many cells of differing types. Our cells differentiate during the development of the embryo to become highly specialised, with each type performing a certain task in the body. There are around 200 different types including skin, nerve, muscle or immune system cells.

Each cell has a fatty membrane outside that encloses a fluid environment – the cytoplasm, a cytoskeleton made of protein filaments, and a nucleus enclosed within a another fatty membrane. Cytoskeletons maintain the shape of a cell, organise the contents, and are used in cell division. The nucleus is home to most of our DNA, the recipe for making proteins, which is arranged into individual genes coding for specific proteins. The production of proteins is also a highly complex process which can be altered by many factors including the nutritional and stress status in an individual.

Proteins

The main work shared almost all cells is to make proteins and energy as required and directed by controlling signals from their environment. Some proteins will be used within the cell they are made in and some will be exported for other cells to use, or to make tissues. Our bodies make most of the proteins that we need, however, some need to be obtained from our diet.

Proteins regulate and maintain cells and are essential for life, acting as enzymes (a catalyst for chemical reactions) and forming the scaffolding for structures such as bones and scar tissue. Some proteins are hormones, which regulate physiology and behaviour and are transported all around the body.

Cytokines

Cytokines are a subset of small proteins that are exported from cells. After leaving the cell they enter the fluid outside, and may then move around in the blood and lymphatic systems. They signal other cells to behave in certain ways after they attach to special receptors in their cell surfaces, with each cytokine having a particular effect that may be altered depending on the presence of other cytokines. Cytokines are especially important for the immune system as they can create inflammation or dampen it down.

Well known inflammatory cytokines include interleukin 1 (IL-1), interleukin 6 (IL-6), tumour necrosis factor α (TNF-α) and transforming growth factor β (TGF-β). These are all significant players in the development and maintenance of arthrofibrosis, with TGF-β being the most important. For more on cytokines see Wikipedia https://en.wikipedia.org/wiki/Cytokine

Inflammation

When injury or surgery occurs many cells are damaged and killed by the trauma. Damaged cells release an “alarm” to signal danger to the rest of the body which stimulates an inflammatory response from other cells via cytokines and related chemokines. These activate an “army” of cells to protect the body from a potential invasion by harmful bacteria and fungi and to clean up the dead and dying cells.

When we experience heat, swelling, redness and pain we are seeing the results of elevated inflammatory cytokines and inflammation. These cytokines are like the bullets fired by an army, and although cytokines are necessary for destroying invading pathogens, they also cause some collateral damage, injuring and killing our own cells. If the body makes these inflammatory cytokines for too long, they can begin to “feed” their own production and that of other inflammatory cytokines, and it becomes very difficult to stop the cascade. It’s as though the army has taken control of the body’s government. The inflammation feeds an ongoing process of scar tissue formation. This is why it is essential to bring the inflammatory process to an end as soon as appropriately possible after surgery.

Image: Inflammation is like a volcano in the joint, with heat and pain radiating from the trauma.

Many types of immune cells and signalling proteins are involved in inflammation, and we won’t attempt to outline them all here. Researchers are still trying to understand the full complexity of their interactions and to discover more effective ways to prevent chronic inflammation.