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The IL-1 families of ligands and receptors exhibit similarity of coding sequences, protein structures, and chromosomal positions, suggesting that they have arisen via duplication of ancestral genes. Within these families there is selectivity in ligand-receptor interactions as well as promiscuity. IL-18 and its receptor are members of these families. IL-18 is recognized as binding to the protein products of the IL18R1 and IL18RAP genes, and with high affinity to a separate IL-18 binding protein (IL-18BP). However, IL-18BP is anomalous, as it exhibits little resemblance to IL-18R proteins. Additionally, IL-18 is produced in the brain in medial habenula neurons, which project IL-18-containing axons to the interpeduncular nucleus. However, there is a lack of focal IL-18R expression in their terminal field. Given these anomalies, we hypothesized that another receptor for IL-18 may exist, and that IL18BP is evolutionarily related to this receptor. We examined Ensembl and National Center for Biotechnology Information databases to identify available IL18BP records (n = 86 species) and show through bioinformatics approaches that across mammalian species with IL18BP genes, IL-18BP is consistently most similar to IL-1R9 (IL-1R accessory protein-like 2), another member of the IL-1R family. IL-1R9 and the related IL-1R8, but not other IL-1R family members, exhibit an amino acid sequence similar to binding site A of human and viral IL-18BPs. Conserved intron/exon boundaries, protein structure, and key binding site amino acids suggest that IL18BP and IL1R9 are evolutionarily related, and that IL-1R9 and IL-1R8 may bind IL-18.

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Interleukin-18 (IL-18) is a pro-inflammatory cytokine which stimulates activation of the nuclear factor kappa beta (NF-κB) pathway via interaction with the IL-18 receptor. The receptor itself is formed from a dimer of two subunits, with the ligand-binding IL-18Rα subunit being encoded by the IL18R1 gene. A splice variant of murine IL18r1, which has been previously described, is formed by transcription of an unspliced intron (forming a 'type II' IL18r1 transcript) and is predicted to encode a receptor with a truncated intracellular domain lacking the capacity to generate downstream signalling. In order to examine the relevance of this finding to human IL-18 function, we assessed the presence of a homologous transcript by reverse transcription-polymerase chain reaction (RT-PCR) in the human and rat as another common laboratory animal. We present evidence for type II IL18R1 transcripts in both species. While the mouse and rat transcripts are predicted to encode a truncated receptor with a novel 5 amino acid C-terminal domain, the human sequence is predicted to encode a truncated protein with a novel 22 amino acid sequence bearing resemblance to the 'Box 1' motif of the Toll/interleukin-1 receptor (TIR) domain, in a similar fashion to the inhibitory interleukin-1 receptor 2. Given that transcripts from these three species are all formed by inclusion of homologous unspliced intronic regions, an analysis of homologous introns across a wider array of 33 species with available IL18R1 gene records was performed, which suggests similar transcripts may encode truncated type II IL-18Rα subunits in other species. This splice variant may represent a conserved evolutionary mechanism for regulating IL-18 activity.

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Effective strategies are urgently required to reduce the prevalence of obesity during growth. Determining which strategies are most successful should also include analysis of their relative costs. To date, few obesity prevention studies in children have reported data concerning cost-effectiveness. The aim of this study was to assess the costs and health benefits of implementing the APPLE (A Pilot Program for Lifestyle and Exercise) project, a 2-year controlled community-based obesity prevention initiative utilizing activity coordinators (ACs) in schools and nutrition promotion in New Zealand children (5-12 years). The marginal costs of the project in 2006 prices were estimated and compared with the kilograms (kg) of weight-gain prevented for children in the intervention relative to the control arm. The children's health-related quality of life (HRQoL) was also measured using the Health Utilities Index (HUI). The total project cost was NZ$357,490, or NZ$1,281 per intervention child for 2 years (NZ$1 = US$0.67 = UK pound 0.35 = EUR euro 0.52). Weight z-score was reduced by 0.18 (0.13, 0.22) units at 2 years and 0.17 (0.11, 0.23) units at 4 years in intervention relative to control children. Mean HUI values did not differ between intervention and control participants. The reduction in weight z-score observed is equivalent to 2.0 kg of weight-gain prevented at 15 years of age. The relatively simple intervention approach employed by the APPLE project was successful in significantly reducing the rate of excessive weight gain in children, with implementation costs of NZ$664-1,708 per kg of weight-gain prevented over 4 years.

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We sought to identify lifestyle behaviours which influence risk of impaired glucose metabolism, IGM (newly diagnosed type 2 diabetes, impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) or insulin resistance (IR) in a predominantly Maori community, and applied the McAuley formula to determine whether it predicts high risk individuals amongst this community. Three hundred and seventy one participants completed a lifestyle and dietary behaviour questionnaire and oral glucose tolerance test. Clinical variables, microalbuminuria, fasting glucose, insulin and lipids were measured. Diabetes, IFG and IGT were defined according to WHO criteria. IR was defined using the McAuley formula. Those with IGM and those with IR showed similar risk factor attributes. Odds ratios (95% CI) for development of IGM and IR were 0.43 (0.21-0.88) and 0.51 (0.33-0.80), respectively, for regular physical activity, and 0.55 (0.26-1.15) and 0.59 (0.37-0.96), respectively, for two or more dietary behaviours characterized by a high intake of fibre. Regular physical activity and a diet characterized by a high intake of dietary fibre were found to reduce risk of newly diagnosed IGM or IR. The McAuley formula appears to predict high-risk individuals in a predominantly Maori population as it does in European populations.

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