The balance between IL-1 and IL-1Ra in disease.

https://www.cell.com/trends/neurosciences/pdf/S0166-2236(00)01661-1.pdf

Interleukin 1 in the brain: biology, pathology and therapeutic target

J Bidwell1, L Keen1, G Gallagher2, R Kimberly3, T Huizinga4, MF McDermott5, J Oksenberg6, J McNicholl7, F Pociot8, C Hardt9 and S D’Alfonso10 Department of Pathology and Microbiology, University of Bristol, Homoeopathic Hospital Site, Cotham, Bristol BS6 6JU, UK; 2University of Glasgow Department of Surgery, Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow G31 2ER, Scotland, UK; Division of Clinical Immunology and Rheumatology, Tinsley Harrison Tower, Room 429, University of Alabama at Birmingham, 1900 University Boulevard, Birmingham, Alabama 35294-0006, USA; Leiden University Medical Center, Department of Rheumatology, C4-R, PO Box 9600, 2300 RC Leiden, The Netherlands; 5Medical Unit, St. Bartholomew’s and the Royal London Hospital School of Medicine and Dentistry, Whitechapel, London E1 1BB, UK; Department of Neurology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0435, USA; Immunology, DASTLR, NCID, CDC MS A25, 1600 Clifton Road NE, Atlanta, Georgia 30333, USA; 8Steno Diabetes Center, Niels Steensensvej 2, DK-2820 Gentofte, Denmark; Institut für Humangenetik, Universitätsklinikum Essen, Hufelandstr. 55, 45122 Essen, Germany; Dipartimento Scienze Mediche, Via Solaroli 17, 28100 Novara, Italy

Cytokine gene polymorphism in human disease: on-line databases, Supplement 1

The interleukin 1 receptor antagonist (IL1Ra) family of molecules now includes one secreted isoform (sIL1Ra) and three intracellular isoforms (icIL1Ra1, 2, and 3). Extensive evidence indicates that the sole biological function of sIL1Ra seems to be to competitively inhibit IL1 binding to cell-surface receptors. Although intracellular IL1Ra1 may be released from keratinocytes under some conditions, the intracellular isoforms of IL1Ra may carry out additional as yet poorly defined roles inside cells. Maintenance of a balance between IL1 and IL1Ra is important in preventing the development or progression of inflammatory disease in certain organs. Both the secreted and intracellular isoforms of IL1Ra contribute to maintenance of this balance. An allelic polymorphism in intron 2 of the IL1Ra gene (IL1RN*2) predisposes to the development or severity of a variety of human diseases largely of epithelial cell origin. Both the impaired production of IL1Ra and the overproduction of IL1β are related to the presence of this allele. Restoration of the balance between IL1Ra and IL1 through a variety of approaches is a therapeutic goal in specific chronic inflammatory diseases.

https://ard.bmj.com/content/annrheumdis/59/suppl_1/i60.full.pdf

Biological role of interleukin 1 receptor antagonist isoforms

Multiple sclerosis: genomic rewards

The A1/A1 genotype of the anti-inflammatory cytokine interleukin 1 receptor antagonist (IL-1Ra) polymorphism was more frequent in 339 Italian MS patients than in healthy controls (HCs) (odds ratio = 1.83). A more aggressive disease course was also associated with A1+ genotypes and might reflect the reduced ability of mononuclear cell cultures of A1+ HCs to produce IL-1Ra. We conclude that an IL-1Ra gene polymorphism is associated with occurrence of disease and clinical course variability in Italian MS patients.

Relevance of interleukin 1 receptor antagonist intron 2 polymorphism in Italian MS patients.

Several genes are likely to predispose to the pathologic changes of MS, but until recently the focus of the genetic search for linkage and associations has been primarily on genes coding for immunorelevant molecules. The factors able to foster the initial changes leading to CNS demyelination in MS patients remain unknown. Head injuries have been considered among them for their potential to open the blood–brain barrier and trigger CNS invasion by immunocytes and demyelination.

Apolipoprotein E (apoE) influences the high-affinity binding of low-density lipoproteins (LDL) to their receptor. This binding regulates the transport and metabolism of cholesterol and phospholipids, two of the major constituent myelin sheets. At least five polymorphisms have been reported in the APOE gene. The e4 allele in the coding region has been associated with several degenerative neurologic diseases, including head trauma and AD.1-2 The recently described AA genotype of the -491 polymorphism in the promoter region3 provides a relative risk …

APOE ε2-4 and -491 polymorphisms are not associated with MS

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Relevance of interleukin 1 receptor antagonist intron 2 polymorphism in Italian MS patients.

APOE ε2-4 and -491 polymorphisms are not associated with MS