The Role of Pro‐Inflammatory Cytokines in Inflammatory Bowel Disease Growth Retardation

Wong, Sze Choong; MacRae, Vicky; McGrogan, Paraic; Ahmed, S Faisal

doi:10.1097/01.mpg.0000226374.18494.14

Cited by 88 publications

(68 citation statements)

References 107 publications

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“…Chronic inflammatory diseases such as juvenile idiopathic arthritis and inflammatory bowel disease often lead to childhood growth retardation through a number of proposed mechanisms that includes nutritional deficiency, chronic inflammation, increased catabolism, defects in the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis and use of glucocorticoids (MacRae et al 2006a, Wong et al 2006. Levels of proinflammatory cytokines, such as tumour necrosis factor (TNF)-a and interleukin (IL)-1b are often raised in these diseases, and measures that block TNF-a action, such as anti-TNF therapy, lead to an improvement in growth.…”

Section: Introductionmentioning

confidence: 99%

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

MacRae¹,

Burdon²,

Ahmed³

et al. 2006

Journal of Endocrinology

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Proinflammatory cytokines inhibit growth plate development. However, their underlying mechanisms of action are unclear. These effects may be mediated by ceramide, a sphingosine-based lipid second messenger, which is elevated in a number of chronic inflammatory diseases. To test this hypothesis, we determined the effects of C2-ceramide, a cell permeable ceramide analogue, on the growth of the ATDC5 chondrogenic cell line and on cultured fetal mice metatarsals. In ATDC5 cells, C2-ceramide significantly induced apoptosis at both 40 (82%; P!0 . 05) and 25 mM (53%; P!0 . 05). At 40 mM, C2-ceramide significantly reduced proliferation ([ 3 H]-thymidine uptake/mg protein) (62%; P!0 . 05). C2-ceramide did not markedly alter the differentiation state of the cells as judged by the expression of markers of chondrogenesis and differentiation (sox 9, collagen II and collagen X). The IGF-I signalling pathway is the major autocrine/paracrine regulator of bone growth. Both in the presence and absence of IGF-I, C2-ceramide (25 mM) induced an equivalent reduction in proliferation (60%; P!0 . 001). Similarly, C2-ceramide (40 mM) induced a 31% reduction in fetal metatarsal growth both in the presence and absence of IGF-I (both P!0 . 001). Furthermore, C2-ceramide reduced ADCT5 proliferation in the presence of AG1024, an IGF-I and insulin receptor blocker. Therefore, C2-ceramide-dependent inhibition appears to be independent of IGF-mediated stimulation of bone growth. Indeed, biochemical studies demonstrated that C2-ceramide (25 mM) pretreatment did not alter IGF-I-stimulated phosphorylation of insulin receptor substrate-1, Akt or P44/42 MAP kinase. In conclusion, C2-ceramide inhibits proliferation and induces apoptosis in growth plate chondrocytes through an IGF-I independent mechanism.

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Section: Introductionmentioning

confidence: 99%

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

MacRae¹,

Burdon²,

Ahmed³

et al. 2006

Journal of Endocrinology

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“…It is only when the lack of the efficacy of such treatment is observed that further diagnostics are conducted, which indicate inflammatory disease of the intestines as the origin of short stature. Overproduction of pro-inflammatory cytokines, including TNF-α, INF-γ, IL-6, IL-12, IL-17, IL-23, and IL-1β, plays a key role in the M Ma ac cr ro o--a an nd d m mi ic cr ro o--n nu ut tr ri ie en nt t d de ef fi ic ci ie en nc ci ie es s N Nu ut tr ri ie en nt ts s P Pe er rc ce en nt ta ag ge e o of f C CD D p pa at ti ie en nt ts s w wi it th h d de ef fi ic ci ie en nc ci ie es s [14] resistance mechanism of tissue resistance to the action of hormonal factor stimulating the growth process [16][17][18]. Studies on animals have documented a pivotal role of IL-6, which induces growth inhibition due to the suppression of IGF-1 secretion.…”

Section: Hormonal and Inflammatory Factorsmentioning

confidence: 99%

“…Inadequate secretion or deficiency of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), GH/IGF-1 axis disturbances as well as tissue resistance to the action of those factors are the main features of hormonal disturbances in children with inflammatory bowel disease [15,16]. Bioavailability of IGF-1 (somatomedin C) depends on its free fraction and on its serum carriers, namely binding proteins (IGFBPs: IGFBP-1 to IGFBP-6).…”

Section: Hormonal and Inflammatory Factorsmentioning

confidence: 99%

Growth retardation in pediatric inflammatory bowel diseases – pathogenesis and treatment

Pytrus¹,

Iwańczak²

2013

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“…Linear growth can be also expressed as height velocity which represents growth status at a particular point of time and might present a more sensitive marker for the impact of disease on normal growth, particularly in peripubertal children. Severe growth impairment has been defined as height velocity SDS below -1 [2].…”

Section: Definition and Prevalencementioning

confidence: 99%

Impact of Therapeutic Strategies on Growth in Pediatric Inflammatory Bowel Disease

Shamir¹

2014

J Clin Cell Immunol

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Growth retardation is a common complication of pediatric inflammatory bowel disease (IBD), which may have long term effects on final adult height and carries significant social and psychological implications. Etiology may be multifactorial including undernutrition, metabolic dysregulation, inflammatory impact on hormonal growth axis and the effect of drugs such as glucocorticoids. Control of disease activity and minimizing the need for corticosteroid therapy are necessary measures in order to facilitate normal growth. However, in many cases these strategies are not sufficient. Currently, there is inconsistent evidence regarding the efficacy of available therapeutic agents to induce long-term effect on growth. The new era of biologic therapies which carries a greater potential to achieve mucosal healing, holds promise for better growth even in children with severe growth impairment. It becomes apparent that prompt recognition of growth impairment combined with aggressive tailored therapeutic approach may offer the best chance for catch-up growth. This review will discuss the definition, prevalence and mechanism of growth retardation in children with IBD and highlight the specific benefits of current therapeutic strategies.

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The Role of Pro‐Inflammatory Cytokines in Inflammatory Bowel Disease Growth Retardation

Cited by 88 publications

References 107 publications

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

Growth retardation in pediatric inflammatory bowel diseases – pathogenesis and treatment

Impact of Therapeutic Strategies on Growth in Pediatric Inflammatory Bowel Disease

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