Lesser known mast cell mediators (Part 5)

Interleukin-16 (IL-16) is a cytokine that attracts several types of cells that express the CD-4 receptor on their surfaces, including monocytes, eosinophils and dendritic cells. It acts by binding to the CD-4 receptor. IL-16 was previously known as lymphocyte chemoattractant factor (LCF).

Interleukin-18 (IL-18) is a cytokine with several defined functions. Working with IL-12, it triggers a cell-mediated immune response after infection. It causes natural killer (NK) cells and some types of T cells to release interferon-γ, and for this reason is sometimes called interferon-γ inducing factor. This interferon activates macrophages and other cell types. IL-18 and IL-12 can inhibit production of IgE and IgG1 when mediated by IL-4. IL-18 causes severe inflammatory reactions and has been implicated in various diseases. In adenomyosis patients, more IL-18 receptors are found in the endometrium. It is one of the molecules responsible for Hashimoto’s thyroiditis. It also increases production of amyloid-beta in neuron cells, which is associated with Alzheimer’s disease.

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that stimulates an acute immune response by binding to CD74. MIF level is associated with severity of rheumatoid arthritis. Glucocorticoids (steroids) stimulate white cells to release MIF.

Transforming growth factor beta (TGF-β) is secreted by mast cells and participates in the pathology of many diseases, including bronchial asthma, heart disease, diabetes, lung fibrosis, telangiectasia, Marfan syndrome, vascular Ehlers Danlos syndrome, Parkinson’s disease, chronic kidney disease, multiple sclerosis, AIDS, among others. (Note: I suspect that one of the links between mast cell disease and EDS is this molecule. Its signaling affects differentiation and regulation of vascular tissues and connective tissues. In a mouse model of Marfan syndrome, a connective tissue disorder, the characteristic Marfan features can be alleviated by administering a TGF- β blocker.)

Tumor necrosis factor (TNF-α) is part of a family of cytokines that cause apoptosis, cell death. It is an adipokine that participates in both general inflammation and the acute phase inflammatory response. It is produced by mast cells as well as many other cell types, including neutrophils, eosinophils and neurons, among others. TNF regulates immune cells, causes fever, weight loss, fatigue and tumor destruction. This molecule is dysregulated in several diseases, including several cancers, severe depression, IBD, Alzheimer’s and rheumatoid arthritis.

Macrophage inflammatory protein 1α (MIP-1α, chemokine ligand 3, CCL3) causes acute inflammation and recruitment of other white blood cells.

Stem cell factor (SCF) is a cytokine that binds to the CD117, better known as CKIT, receptor on mast cells. SCF regulates the mast cell life cycle, telling them when to make new cells and when to die. In CKIT+ mast cell patients, the CKIT receptor is misshapen so the cell mistakenly thinks SCF is bound to the receptor all the time. It also induces histamine release.

 

All mediators listed here are produced by mast cells upon stimulation and are not stored in granules.