Immunology

See Also

• Toll-like receptors (TLRs)
• Interleukin-6 (IL-6)
• Cytokines
• Growth Factors

Description

IL-1 is one of the most important immune modifying interleukins. The predominant function of IL-1 is to enhance the activation of T lymphocytes in response to antigen.

Discussion

Interleukin-1 (IL-1) is a cytokine that is secreted by macrophages, monocytes and dendritic cells. It is an important part of the inflammatory response of the body against infection. It increases the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes, the cells that fight pathogens, to sites of infection. It also re-sets the hypothalamus thermoregulatory center, leading to an increased body temperature which expresses itself as fever. It is therefore called an endogenous pyrogen. The increased body temperature helps the body's immune system to fight infection.

There are a few molecules of the IL-1 family. The two most studied molecular forms of interleukin-1, are:

• IL-1α
• IL-1β

For the most part, these two forms of IL-1 bind to the same cellular receptor. This receptor is composed of two related, but non-identical, subunits that transmit intracellular signals via a pathway that is mostly shared with certain other receptors. These include the Toll family of innate immune receptors and the receptor for IL-18.

The IL-1 receptor antagonist, IL-1Ra, is an agent which binds to the same receptor on the cell surface as IL-1, and thus prevents IL-1 from sending a signal to that cell. It is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role. It is commercially produced as anakinra, which is a human recombinant form of IL-1Ra.

Abstracts

Interleukin-1 gene cluster polymorphisms are associated with nutritional status and inflammation in patients with end-stage renal disease.

Blood Purif. 2005;23(5):384-93. Epub 2005 Jul 27. Maruyama Y, Nordfors L, Stenvinkel P, Heimburger O, Barany P, Pecoits-Filho R, Axelsson J, Hoff CM, Holmes CJ, Schalling M, Lindholm B.

• BACKGROUND: Wasting and inflammation are two common risk factors for death in patients with end-stage renal disease (ESRD). Interleukin-1beta (IL-1beta) and its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of wasting and inflammation. METHODS: To investigate effects of the IL-1 gene cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients (52+/- 12 years, 62% males) close to the start of renal replacement therapy. 205 healthy volunteers served as controls. We analyzed the IL-1B -511C/T, -31C/T, and +3954C/T polymorphisms as well as a variable number of a tandem repeat (VNTR) in IL-1RN. Nutritional parameters included serum albumin level, subjective global nutritional assessment (SGA), and body composition evaluated by dual-energy X-ray absorptiometry (DXA). We used serum high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation. RESULTS: Wasting (SGA>1) was present in 31%, whereas inflammation (CRP>/=10 mg/l) was present in 36% of the patients. The male carriers of the -511T/T and -31C/C genotypes had a lower prevalence of wasting (p<0.05), higher body mass index (BMI) (p<0.05), and higher lean body mass (LBM) (p<0.01). In a stepwise multiple regression model, age (p<0.05), BMI (p<0.01) and the IL-1B -511 genotype (p<0.01) were independently associated with LBM. The carriers of the +3954T allele had a lower prevalence of inflammation (p<0.05) and lower serum hsCRP (p<0.05). The VNTR in IL-1RN was not associated with any markers. CONCLUSION: The investigated IL-1 gene cluster polymorphisms were associated with nutritional status and inflammation in ESRD patients, but marked differences were found between the genders. These polymorphisms could have prognostic utility for predicting wasting and inflammation in ESRD patients.