A Preliminary Study of Growth Hormone Therapy for Crohn's Disease

Slonim, Alfred E.; Bulone, Linda; D'Amore, M; Goldberg, Teresia; Wingertzahn, Mark A.; McKinley, Matthew

doi:10.1056/nejm200006013422203

Cited by 187 publications

(109 citation statements)

References 18 publications

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“…14 Indeed, a clinical trial in patients with active CD reported that GH therapy decreased the CDAI score and reduced the need for other medications. 24 IBD is frequently complicated by growth failure in children and wasting in adults. [2][3][4] Although IBDassociated malnutrition is considered the main source of these complications, 5 recent evidence in IBD animal models suggests a direct adverse effect of systemic inflammation on the GH/IGF-1 axis.…”

Section: Discussionmentioning

confidence: 99%

Infliximab reverses growth hormone resistance associated with inflammatory bowel disease

Gentilucci¹,

Caviglia

Picardi³

et al. 2005

Aliment Pharmacol Ther

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SUMMARYBackground: Increasing evidence shows that inflammation plays a major role in the aetiology of catabolism and wasting observed in inflammatory bowel disease via growth hormone resistance. Aim: To evaluate the effect of infliximab treatment on the growth hormone/insulin-like growth factor-1 axis. Methods: Fourteen adults with active Crohn's disease or ulcerative colitis underwent three infliximab infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance infusions 8 weeks apart. Blood samples were collected for the analysis of serum growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3 and acid labile subunit. Results: Serum insulin-like growth factor-1 and insulinlike growth factor-binding protein-3 concentrations, which were significantly lower in inflammatory bowel disease patients before treatment compared with con-

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Section: Discussionmentioning

confidence: 99%

Infliximab reverses growth hormone resistance associated with inflammatory bowel disease

Gentilucci¹,

Caviglia

Picardi³

et al. 2005

Aliment Pharmacol Ther

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“…2,39,40 Here, we have demonstrated that peripheral activation of the mu opioid pathway protects against DSS-induced intestinal injury and enhances wound healing. We have shown that the MORspecific agonist DALDA activates proliferative signaling in the intestine, a response associated with enhanced colonocyte-derived Stat3 activation and induction of cytoprotective genes.…”

Section: Discussionmentioning

confidence: 91%

Mu Opioid Signaling Protects Against Acute Murine Intestinal Injury in a Manner Involving Stat3 Signaling

Goldsmith

Uronis

Jobin

2011

The American Journal of Pathology

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Opiates have long been used as analgesics to relieve pain associated with various medical conditions. Here, we evaluated the effect and mechanism of mu opioid signaling on the intestinal wound healing response and assessed downstream pathways known to be protective against intestinal injury. Mice (C57BL/6) were exposed to 3% dextran sodium sulfate (DSS) for 7 days or 4% DSS for 5 days followed by 7 days of water. The mu opioid receptor (MOR)-specific agonist [D-Arg2,Lys4]dermorphin-(1,4)-amide (DALDA) and the antagonist cyprodime were injected s.c. daily for in vivo studies or used for in vitro analysis. We found that MOR activation attenuated DSS-induced histologic and gross intestinal injury and weight loss; diminished Ifng, Tnf, and Il6 mRNA expression; and promoted intestinal healing during recovery. DALDA also enhanced colonocyte proliferation (Ki-67 staining) by 350%. MOR activation increased Stat3 phosphorylation in both DALDA-treated mice and the CMT-93 cell line. Importantly, DALDAinduced colonocyte migration was completely ablated by shStat3 knockdown. Together, this work shows that MOR activation protects against and enhances recovery from DSS-induced intestinal injury. This is associated with an increase in Stat3 activation. Furthermore, Stat3 is required for DALDA-induced colonocyte migration. Consequently, manipulation of MOR signaling may represent a novel means to promote mucosal healing and to maintain intestinal homeostasis after intestinal injury.

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“…For example, recombinant human growth hormone induced protective effects in TNBS-induced colitis [309]. A preliminary study showed that human growth factor was effective in CD, it improved the clinical symptoms (the number of liquid/soft stools, severity of abdominal pain and overall well being) and a statistically significant increase in circulating levels of IGF-1 was observed [310]. Further, placebo controlled human studies should be performed to determine the real place of growth factor in the therapy of IBD.…”

Section: Growth Hormone (Gh)mentioning

confidence: 99%

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires¹,

Tóth²,

Zádori

2014

CPD

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Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The two main forms of IBD are Crohn's disease and ulcerative colitis. According to the recent concept the disease is caused by a combination of factors, including genetics, immune dysregulation, barrier dysfunction and the change in microbial flora. Environmental factors, such as changes in diet, antibiotic use, smoking or improved domestic hygiene (e.g. eradication of intestinal helminths) probably contribute to the development and increased prevalence of IBD. Dysregulation of mucosal immunity in IBD causes an overproduction of inflammatory cytokines which resulted in uncontrolled intestinal inflammation. Based on extensive research over the last decade, besides the conventional therapy, there are several novel pathways and specific targets, on which focus new therapeutics. New therapeutics aim 1./ to correct genetic susceptibility by stimulating NOD2 expression, TLR3 signaling or inhibition of TLR4 pathway, 2./ to restore the immune dysregulation by inhibition of pro-inflammatory cytokines (TNF-, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10, IL-11, IFN--1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF, KGF, TGF-, VEGF, 4./ to restore the normal bacterial flora by antibiotics, probiotics. However, in spite of these numerous potential targets, the true value and clinical significance of most of the new biologics and molecules are not clear yet.

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A Preliminary Study of Growth Hormone Therapy for Crohn's Disease

Abstract: Our preliminary study suggests that growth hormone may be a beneficial treatment for patients with Crohn's disease.

Cited by 187 publications

References 18 publications

Infliximab reverses growth hormone resistance associated with inflammatory bowel disease

Infliximab reverses growth hormone resistance associated with inflammatory bowel disease

Mu Opioid Signaling Protects Against Acute Murine Intestinal Injury in a Manner Involving Stat3 Signaling

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

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