IGF-1 and ADMA Levels Are Inversely Correlated in Nondiabetic Ankylosing Spondylitis Patients Undergoing Anti-TNF-Alpha Therapy

Like rheumatoid arthritis, ankylosing spondylitis (AS) is also an inflammatory disease associated with accelerated atherosclerosis and the presence of metabolic syndrome (MeS) features. AS patients often display osteoporosis as well as new bone formation. Insulin-like growth factor 1 (IGF-1) is a protein involved in both inflammation and bone metabolism. In the present study we assessed whether disease activity, systemic inflammation, MeS features, adipokines, and biomarkers of endothelial activation were associated with IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels in a series of 30 nondiabetic AS patients without CV disease undergoing TNF-αantagonist-infliximab therapy. All determinations were made in the fasting state, immediately before an infliximab infusion. Although no association of IGF-1 and IGFBP-3 levels with angiopoietin-2 or osteopontin was found, an inverse correlation between IGF-1 levels and asymmetric dimethylarginine (ADMA), an endogenous endothelial nitric oxide synthase inhibitor that impairs nitric oxide production and secretion promoting endothelial dysfunction, was found (r=-0.397;P=0.04). However, no significant association was found between IGF-1 and IGFBP-3 levels and disease activity, systemic inflammation, metabolic syndrome features, or adipokines. In conclusion, in nondiabetic patients with AS undergoing periodic anti-TNF-αtherapy, IGF-1 and ADMA are inversely correlated.

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Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

Mediators of Inflammation ◽

10.1155/2014/798060 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Fernanda Genre ◽

Raquel López-Mejías ◽

Javier Rueda-Gotor ◽

José A. Miranda-Filloy ◽

Begoña Ubilla ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Disease Activity ◽

Systemic Inflammation ◽

Inverse Correlation ◽

Chronic Inflammatory Disease ◽

Compensatory Mechanism ◽

Infliximab Infusion ◽

Potential Biomarker ◽

Marginal Association ◽

Cv Disease

Objective. TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-αantagonist infliximab therapy and if infliximab infusion modified TRAIL levels.Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-αtherapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-αinfusion were analyzed.Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-αinfusion did not change TRAIL levels after 120′.Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients.

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Comparative study of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) level and ratio measurements and their relationship with an index of clinical activity in the management of patients with acromegaly

Metabolism ◽

10.1016/s0026-0495(97)90183-9 ◽

1997 ◽

Vol 46 (5) ◽

pp. 494-498 ◽

Cited By ~ 16

Author(s):

Concepción Páramo ◽

M.Amalia Andrade O ◽

Enrique Fluiters ◽

Reyes Luna ◽

Javier de la Fuente ◽

...

Keyword(s):

Growth Factor ◽

Comparative Study ◽

Binding Protein ◽

Clinical Activity ◽

Insulin Like Growth Factor ◽

Factor I ◽

Igf I ◽

Igf Binding ◽

Igf Binding Protein ◽

Igfbp 3

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Specimen processing time and measurement of total insulin-like growth factor-I (IGF-I), free IGF-I, and IGF binding protein-3 (IGFBP-3)

Growth Hormone & IGF Research ◽

10.1016/j.ghir.2006.01.002 ◽

2006 ◽

Vol 16 (2) ◽

pp. 86-92 ◽

Cited By ~ 15

Author(s):

Tiffany G. Harris ◽

Howard D. Strickler ◽

Herbert Yu ◽

Michael N. Pollak ◽

E. Scott Monrad ◽

...

Keyword(s):

Growth Factor ◽

Processing Time ◽

Binding Protein ◽

Insulin Like Growth Factor ◽

Factor I ◽

Igf I ◽

Specimen Processing ◽

Igf Binding ◽

Igf Binding Protein ◽

Igfbp 3

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Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4

Journal of Endocrinology ◽

10.1677/joe.0.1360091 ◽

1993 ◽

Vol 136 (1) ◽

pp. 91-104 ◽

Cited By ~ 119

Author(s):

L. R. Donahue ◽

W. G. Beamer

Keyword(s):

Body Composition ◽

Growth Factor ◽

Gh Deficiency ◽

Body Water ◽

Insulin Like Growth Factor ◽

Gh Therapy ◽

Factor I ◽

Igf I ◽

Body Compartments ◽

Igfbp 3

ABSTRACT Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments – water, fat, protein and mineral – are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38–130 μg/l) compared with normal lit/+ littermates (range 432–567 μg/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I. Changes in mineral observed in lit/lit mice could be the result of action by GH, IGF-I or both hormones. Therefore, when GH is chronically manipulated by GH deficiency as in lit/lit mice, by GH excess as in acromegaly, or by GH therapy, all four body compartments are affected, suggesting that GH therapy is most valuable when the treatment goal is to alter overall body composition. Journal of Endocrinology (1993) 136, 91–104

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