Systemic inflammation
Encyclopedia
Chronic systemic inflammation (SI) is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system.

It can contribute to the development or progression of certain conditions.

Mechanisms Inducing SI

Release of pro-inflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s and activation of the innate immune system may be the result of either external (biological or chemical agents) or internal (genetic mutations/variations) factors.

Lack of Control by Tolerogenic Dendritic Cells and T-regulatory Cells

While SI may be induced by multiple external factors, research suggests that a lack of control by tolerogenic dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s and T-regulatory cells (Treg) is possibly the primary risk factor for the development of SI. In functioning immune responses, T-helper and T-cytotoxic cells are activated by presentation of antigens by antigen-presenting cell
Antigen-presenting cell
An antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...

s (APCs). Chief among these are dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s (DCs). When a DC presents an antigen to a Treg cell, a signal is then sent to the nucleus of the DC, resulting in the production of Indoleamine 2,3- Dioxygenase (IDO). IDO inhibits T cell responses by depleting tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

 and producing kynurenine
Kynurenine
L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.Kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid...

, which is toxic to the cell.

Individuals susceptible to developing chronic systemic inflammation appear to lack proper functioning of Treg cells and TDCs. In these individuals, a lack of control of inflammatory processes results in multiple chemical and food intolerances, autoimmune diseases and many other symptoms and diseases.
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