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Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a member of the TGF-b superfamily, previously studied in cancer and inflammation. In addition to regulating body weight, MIC-1/GDF15 may be used to predict mortality and/or disease course in cancer, cardiovascular disease, chronic renal and heart failure, as well as pulmonary embolism. These data suggested that MIC-1/GDF15 may be a marker of all-cause mortality. To determine if serum MIC-1/GDF15 estimation is a predictor of all-cause mortality we examined a cohort of 876 male subjects aged 35 to 80 years, selected from the Swedish Population Registry, and followed them for overall mortality. Serum MIC-1/GDF15 levels were determined for all subjects from samples taken at study entry. A second (independent) cohort of 324 same-sex twins (69% female) from the Swedish Twin Registry was similarly examined. All the twins had telomere length measured and 183 had serum levels of interleukin 6 (IL-6) and C reactive protein (CRP) available. Patients were followed for up to 14 years and had cause specific and all-cause mortality determined. Serum MIC-1/GDF15 levels predicted mortality in the all-male cohort with an adjusted odds ratio of death of 3.38 (95%CI 1.38-8.26). This finding was validated in the twin cohort. Serum MIC-1/GDF15 remained an independent predictor of mortality when further adjusted for telomere length, IL-6 and CRP. Additionally, serum MIC-1/GDF15 levels were directly correlated with survival time independently of genetic background. Serum MIC-1/GDF15 is a novel predictor of all-cause mortality.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Surgery and Preoperative Sciences, Urology, Umeå University, Umeå, Sweden St Vincent's Centre for Applied Medical research, St Vincent's Hospita
This article was published in the following journal.
Name: Aging cell
Macrophage inhibitory cytokine-1 (MIC-1), a transforming growth factor-β superfamily cytokine, is involved in tumor pathogenesis, and its measurement can be used as a clinical tool for the diagnosis ...
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A suppressor of cytokine signaling protein that consists of an N-terminal kinase-inhibitory region, a central SH2 DOMAIN, a characteristic C-terminal SOCS box (a 40-amino acid motif, which functions to recruit E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES). SOCS3 inhibits cytokine signaling by binding to RECEPTOR PROTEIN-TYROSINE KINASES as well as CYTOKINE RECEPTOR GP130; ERYTHROPOIETIN RECEPTORS; INSULIN RECEPTOR; and the LEPTIN RECEPTOR. Its functions include suppression of ERYTHROPOIESIS in the fetal liver.
An INTERLEUKIN-6 related cytokine that exhibits pleiotrophic effects on many physiological systems that involve cell proliferation, differentiation, and survival. Leukemia inhibitory factor binds to and acts through the lif receptor.
A receptor subunit that combines with CYTOKINE RECEPTOR GP130 to form the dual specificity receptor for LEUKEMIA INHIBITORY FACTOR and ONCOSTATIN M. The subunit is also a component of the CILIARY NEUROTROPHIC FACTOR RECEPTOR. Both membrane-bound and secreted isoforms of the receptor subunit exist due to ALTERNATIVE SPLICING of its mRNA. The secreted isoform is believed to act as an inhibitory receptor, while the membrane-bound form is a signaling receptor.
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