<unk>  was thought to be produced primarily by macrophages, but it is produced also by a broad variety of cell types including lymphoid cells, mast cells, endothelial cells, cardiac myocytes, adipose tissue, fibroblasts, and neurons. Large amounts of<unk>  are released in response to lipopolysaccharide, other bacterial products, and interleukin-1 (IL-1). In the skin, mast cells appear to be the predominant source of pre-formed<unk> , which can be released upon inflammatory stimulus (e.g., LPS). It has a number of actions on various organ systems, generally together with IL-1 and interleukin-6 (IL-6): * On the hypothalamus: * Stimulation of the hypothalamic-pituitary-adrenal axis by stimulating the release of corticotropin releasing hormone (CRH) * Suppressing appetite * Fever * On the liver: stimulating the acute phase response, leading to an increase in C-reactive protein and a number of other mediators. It also induces insulin resistance by promoting serine-phosphorylation of insulin receptor substrate-1 (IRS-1), which impairs insulin signaling * It is a potent chemoattractant for neutrophils, and promotes the expression of adhesion molecules on endothelial cells, helping neutrophils migrate. * On macrophages: stimulates phagocytosis, and production of IL-1 oxidants and the inflammatory lipid prostaglandin E2 (PGE2) * On other tissues: increasing insulin resistance.<unk>  phosphorylates insulin receptor serine residues, blocking signal transduction. * On metabolism and food intake: regulates bitter taste perception. A local increase in concentration of<unk>  will cause the cardinal signs of Inflammation to occur: heat, swelling, redness, pain and loss of function. Whereas high concentrations of<unk>  induce shock-like symptoms, the prolonged exposure to low concentrations of<unk>  can result in cachexia, a wasting syndrome. This can be found, for example, in cancer patients. Said et al. showed that<unk>  causes an IL-10-dependent inhibition of CD4 T-cell expansion and function by up-regulating PD-1 levels on monocytes which leads to IL-10 production by monocytes after binding of PD-1 by PD-L. The research of Pedersen et al. indicates that<unk>  increase in response to sepsis is inhibited by the exercise-induced production of myokines. To study whether acute exercise induces a true anti-inflammatory response, a model of 'low grade inflammation' was established in which a low dose of E. coli endotoxin was administered to healthy volunteers, who had been randomised to either rest or exercise prior to endotoxin administration. In resting subjects, endotoxin induced a 2- to 3-fold increase in circulating levels of<unk> . In contrast, when the subjects performed 3 hours of ergometer cycling and received the endotoxin bolus at 2.5 h, the<unk>  response was totally blunted. This study provides some evidence that acute exercise may inhibit<unk>  production. In the brain<unk>  can protect against excitotoxicity.<unk>  strengthens synapses.<unk>  in neurons promotes their survival, whereas<unk>  in macrophages and microglia results in neurotoxins that induce apoptosis.<unk> -α and IL-6 concentrations are elevated in obesity. Monoclonal antibody against<unk> -α is associated with increases rather than decreases in obesity, indicating that inflammation is the result, rather than the cause, of obesity.<unk>  and IL-6 are the most prominent cytokines predicting COVID-19 severity and death.
Tumor necrosis factor
Interleukin
Major basic protein
Macrophage-activating factor
Defensin
Leukotriene
Lymphokine
Nitric oxide