Anakinra as an interleukin 1 receptor antagonist, complicated genetics and molecular impacts--from the point of view of mouse genomics

Abstract

IL-1 receptor antagonist (IL-1rn) is a protein that binds to IL-1 receptors (IL-1r1) and inhibits the binding of IL-1α and IL-1β. In recent years, IL-1rn has been implicated to be associated with many human health problems. The effects of treatment of several inflammatory disorders with anakinra, which is an interleukin-1 (IL-1) receptor antagonist, have also been reported. Both positive and negative effects have been described. In this review, we systematically analyzed the expression, correlation, and regulation of IL-1rn and its 13 partner genes using available gene expression profiles from a variety of tissues in a well known transcriptome database, Genenetwork. The 13 partner genes include IL-1r1, IL-1β, IL-1α, Myd88, Irak1, Irak2, Irak4, Traf6, Tlr4, IL-1rap, Ikbkap, Nfkb1, and Nfkb2. Gene expression profiles are from 10 tissues including spleen, kidney, lung, whole brain, eye, prefrontal cortex, cerebellum, hippocampus, striatum, and nucleus accumbens. Our analysis indicated that the interactions among IL-1rn and its partner are complex and different from tissues to tissues, suggesting a broad spectrum of the effect of IL-1rn on biological and metabolic pathways. Transcripts and protein sequences resulted from different splicing, interaction with genomic background of individuals, and environmental factors affect function of IL-1rn. At present, our knowledge on the function of IL-1rn and its partner in various tissues or organs is very limited. The long term and extended effect of anakinra on human health needs further investigations. In the future, targeted sequences or oligos of Il-1rn might be ideal for therapeutic application with less toxic and more specific in the treatment of specific disease. Detailed study on the molecular function of IL-1rn and its interaction with other genes and environmental factors is essential for development therapeutic application using IL-1rn.

Fig. 1

Potential gene network of IL-1rn. Data are generated using STRING 9.0. Nodes are colored for predicted functional links. Stronger associations are represented by thicker lines.

Fig. 2

Transcriptome maps of two probes of IL-1r1 and three probes of IL-1rn between female and male kidneys. Probes are from the M430.v2 chip of Affymetrix. The two probes of IL-1r1 are probe ID 1448950 and ID 1459777. The three probes of IL-1rn are ID 1451798, ID 1423017, and ID 1425663. KidneyM45=transcriptome mapping generated from gene expression profiles of kidneys of male mice from 45 BXD strains. Kidney F 65=transcriptome mapping generated from gene expression profiles of kidneys of female mice from 65 BXD strains.