How does the inflammatory response end?

Immune cells produce anti-inflammatory cytokine mediators that help to suppress the inflammatory response and suppress the production of pro-inflammatory cytokines. The natural anti- inflammatory cytokines are Interleuken-1 receptor antagonist (IL-1ra), Interleukin –10, Interleukin –4, Interleukin –13 and transforming growth factor-beta1 (TGF-beta1). Research has shown that administration of these anti-inflammatory cytokines prevents the development of painful nerve pain that is produced by a naturally occurring irritant protein called Dynorphin A [30] [13]

Under normal circumstances,, the inflammatory response should only last for as long as the infection or the tissue injury exists. Once the threat of infection has passed or the injury has healed, the area should return to normal existence.

One of the ways that the inflammatory response ends is by a phenomenon known as “Apoptosis”..

Most of the time, cells of the body die by being irreparably damaged or by being deprived of nutrients. This is known as Necrotic death. However, cells can also be killed in another way, i.e. by “committing suicide”. On receipt of a certain chemical signal, most cells of the body can destroy themselves. This is known as Apoptotic death. There are two main ways in which cells can commit Apoptosis.

1. By receiving an Apoptosis signal. When an chemical signal is received that indicates that the cell should kill itself, it does so.

2. By not receiving a “stay-alive” signal. Certain cells, once they reach an activated state, are primed to kill themselves automatically within a certain period of time, i.e. to commit Apoptosis, unless instructed otherwise. However, there may be other cells that supply them with a “stay-alive” signal, which delays the Apoptosis of the cell. It is only when the primed cell stops receiving this “stay-alive” signal that it kills itself.

The immune system employs method two above. The immune cells involved in the inflammatory response, once they become activated, are primed to commit Apoptosis. Helper T cells emit the stay-alive signal, and keep emitting the signal for as long as they recognize foreign antigens or a state of injury in the body, thus prolonging the inflammatory response. It is only when the infection or injury has been eradicated, and there is no more foreign antigen that the helper T cells stop emitting the stay-alive signal, thus allowing the cells involved in the inflammatory response to die off.

If foreign antigen is not eradicated from the body or the injury has not healed, or the helper T cells do not recognize that fact, or if the immune cells receive the stay-alive signal from another source, then chronic inflammation may develop.

The final pathway for the natural suppression of the inflammatory response is in the spinal cord where there is a complex network of inhibitory neurons (‘gate control’) that is driven by descending projections from brain stem sites. These inhibitory neurons act to dampen and counteract the spinal cord hyper excitability produced by tissue or nerve injury. Thus, peripherally evoked pain impulses pass through a filtering process involving inhibitory transmitters gamma-aminobutyric acid (GABA), glycine and enkephalins. The activity of these substances in the spinal cord usually attenuates and limits the duration of pain. In the case of persistent pain, there is evidence of pathological reduction of the supraspinal inhibitory actions in combination with ectopic afferent input in damaged nerves [31] .