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. Excessive amounts of proinflammatory cytokines have been shown to cause detrimental effects. The kidney
proximal tubule cells produce proinflammatory cytokines in response to
lipopolysaccharide. Proinflammatory cytokines affect the renal K+ channels. IFNγ causes delayed suppression and acute stimulation of the 40 pS K+ channel. Also,
transforming growth factor beta 1 (TGF-β1) activates the calcium-activated potassium channel (
KCa3.1) which could be involved the detrimental effects of renal
fibrosis.
Graft-vs-host disease 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. 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,
TH1,
TH2, or
TH17 phenotypes. Both CD4+ and CD8 IL-17 producing T cells have been shown to cause aTH1, causing tissue inflammation and resulting in severe GVHD.
In cystic fibrosis A proinflammatory cytokine causes hyperinflammation, the leading cause of lung tissue destruction in
cystic fibrosis. 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). 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.
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. Recent studies have shown the ability of exercise to control
oxidative stress and inflammation in cardiovascular disease.
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. 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.
In osteoarthritis TNF-α, IL-1 and IL-6 have been found to play a pivotal role in
cartilage matrix degradation and
bone resorption in
osteoarthritis. Animal studies indicate that inflammatory cytokines may stimulate
chondrocytes to release cartilage-degrading
protease in osteoarthritis. This finding does not, however, necessarily translate to
Homo sapiens, as osteoarthritis in humans is considered to be more complex than any animal model.
Fatigue Cytokines have key roles in inflammation, which is seen as a causal mechanism in
fatigue. == Clinical implications ==