Inflammatory cytokine

An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule (a

Excessive chronic production of inflammatory cytokines contribute to

Therapies to treat inflammatory diseases include monoclonal antibodies that either neutralize inflammatory cytokines or their receptors.

Definition

An inflammatory cytokine is a type of

Due to its proinflammatory action, a proinflammatory cytokine tends to make the disease itself or the symptoms correlated to a disease worse by causing fever, inflammation, tissue destruction, and in some cases, even shock and death.^[7] Excessive amounts of proinflammatory cytokines have been shown to cause detrimental effects^[2]

In the kidney

A proinflammatory cytokine affects functions of transporters and

Graft-versus-host disease (GvHD) targets JAK 1 and 2, the human tyrosine kinase protein required for signaling in multiple cytokines. When these kinases are activated, signal proteins of the signal transducer and activator of transcription (STAT) protein family – which include transcription factors for target genes that serve proinflammatory roles – are phosphorylated.^[9] The severity of GvHD is highly variable and is influenced by the amount of native cells present in the environment along with other regulatory T cells, T_H1, T_H2, or T_H17 phenotypes.^[10] Both CD4⁺ and CD8 IL-17 producing T cells have been shown to cause aTH1, causing tissue inflammation and resulting in severe GVHD.^[11]

In cystic fibrosis

A proinflammatory cytokine causes hyperinflammation, the leading cause of lung tissue destruction in cystic fibrosis.^[12] With such a strong inflammatory response and an elevated number of immune cells, lungs of cystic fibrosis patients cannot clear the bacteria and become more susceptible to infections. A high prevalence (40-70%) of patients with cystic fibrosis show signs of asthma, possibly due to the primary deficiency in the cystic fibrosis transmembrane conductance regulator (CFTR).^[13] CFTR-deficient T-helper cells create an inflammatory environment that has high concentrations of TNF-α, IL-8, and IL-13, which contributes to increased contractility of airway smooth muscle.^{[citation needed]}

In cardiovascular disease

Atherosclerosis induces a dysfunctional endothelium, which recruits immune cells that form lesions. Proinflammatory mediators cause inflammation after ligands in the heart vasculature activate immune cells.^[14] Recent studies have shown the ability of exercise to control oxidative stress and inflammation in cardiovascular disease.^{[citation needed]}

In adipose tissue metabolism and obesity

A proinflammatory cytokine may be present in adipose tissues. Adipocytes generate TNF-α and other interleukins. Cytokines derived from adipose tissue serve as remote regulators such as hormones. Studies have shown that TNF-α and IL-6 concentrations are elevated in obesity.^[15][16][17] Obesity leaves an excess of nutrients for the body, thereby causing adipocytes to release more proinflammatory cytokines. Classically activated macrophages in the visceral fat accumulate in the fat tissues and continuously release proinflammatory cytokines, causing chronic inflammation in obese individuals.^{[citation needed]}

In osteoarthritis

TNF-α, IL-1 and IL-6 have been found to play a pivotal role in

Cytokines have key roles in inflammation, which is seen as a causal mechanism in fatigue.^[20][21]

Clinical implications

Reducing the biological activity of proinflammatory cytokine can reduce the brunt of attack from diseases.^[7]

Blocking IL-1 or TNF-α has been highly successful in helping patients with rheumatoid arthritis,

Estrogen has been shown to promote healing by decrease the production of various proinflammatory cytokines like IL-6,^[24] TNF-α,^[25] and macrophage migration inhibitory factor (MIF). Increased MIF levels are often found at the site of chronic non-healing ulcers, with those levels dropping significantly with successful healing. A 2005 review of current experimental data shows that "estrogen regulates healing almost exclusively via MIF down-regulation and identifies novel MIF-regulated gene targets and clusters associated with aberrant healing." By down-regulating MIF, estrogen can promote healing, as correlated by clinical studies on aging skin and skin wounds. Unfortunately, estrogen-therapy has known carcinogenic effects^[26] as mentioned by the American Cancer Society (increased incidences of breast cancer in women who undergo HRT). However, scientists could make important discoveries in the future by studying "downstream effects on genes/factors that mediate the effects of estrogen on healing."^[27]

Histone deacetylate inhibitors (HDACi) can suppress proinflammatory cytokine production and reduce GvHD.^{[citation needed]}

Some research also suggest an immunoregulatory effect of vitamin D, which has been shown to reduce the secretion of specific inflammatory cytokines.^[28][29]

References