Inflammatory cytokines: from discoveries to therapies in IBD

Marafini, Irene; Sedda, Silvia; Dinallo, Vincenzo; Monteleone, Giovanni

doi:10.1080/14712598.2019.1652267

Cited by 115 publications

(97 citation statements)

References 134 publications

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“…Among the investigated cytokines, notable results have been obtained for IL-6. The possibility of predicting clinical response to biological therapy would be an extremely valuable tool [29]. Moreover, considering that several anti-cytokine compounds are now available for the treatment of patients with IBD [30], the identification of a biomarker that could broadly predict therapy response irrespective of the type of biologic is of crucial relevance.…”

Section: Discussionmentioning

confidence: 99%

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

Caviglia

Rosso

Stalla

et al. 2020

JCM

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In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.

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Section: Discussionmentioning

confidence: 99%

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

Caviglia

Rosso

Stalla

et al. 2020

JCM

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“…Current evidence suggests that immune disorders contribute to the IBD process via cytokine production in bowel lesions. Many proinflammatory cytokines, such as TNF- α and IL-1/6/22/23, and anti-inflammatory cytokines (such as IL-10) have been studied to determine their roles in IBD [ 30 ]. For example, it was found that IL-1 is highly activated in IBD patients and that IL-1 β activates CD4+ T cells [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

Zheng

et al. 2020

Mediators of Inflammation

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Inflammatory bowel disease, a gut disease that is prevalent worldwide, is characterized by chronic intestinal inflammation, such as colitis, and disorder of the gut microbiome. Glycine (Gly) is the simplest amino acid and functions as an anti-inflammatory immune-nutrient and intestinal microbiota regulator. This study aimed at investigating the effect of Gly on colitis induced in mice by intrarectal administration of 5% acetic acid (AA). Bodyweight and survival rates were monitored, and colonic length and weight, serum amino acid concentrations, intestinal inflammation-related gene expression, and colonic microbiota abundances were analyzed. The results showed that Gly dietary supplementation had no effect on the survival rate or the ratio of colonic length to weight. However, Gly supplementation reversed the AA-induced increase in serum concentrations of amino acids such as glutamate, leucine, isoleucine, and valine. Furthermore, Gly inhibited colonic gene expression of interleukin- (IL-) 1β and promoted IL-10 expression in colitis mice. Gly supplementation also reversed the AA-induced reduction in the abundance of bacteria such as Clostridia, Ruminococcaceae, and Clostridiales. This change in the intestinal microbiota was possibly attributable to the changes in colonic IL-10 expression and serum concentrations of valine and leucine. In sum, Gly supplementation regulated the serum concentrations of amino acids, the levels of colonic immune-associated gene expression, and the intestinal microbiota in a mouse model of colitis. These findings enhance our understanding of the role of Gly in regulating metabolism, intestinal immunity, and the gut microbiota in animals afflicted with colitis.

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“…Pro-inflammatory cytokines, which mediate interaction between immune cells and non-immune cells, contribute to the inflammatory status of the intestine. Accumulating evidence suggests that cytokines may be useful for predicting the response to anti-TNF therapy (164). CD patients with low serum baseline concentrations of IL-1β (<0.64 pg/ml) were more likely to achieve infliximab (IFX) response (44).…”

Section: Biomarkers Predicting Clinical Response Pro-inflammatory Cytmentioning

confidence: 99%

Serum Biomarkers for Inflammatory Bowel Disease

et al. 2020

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Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed. Recently, serum biomarkers have made a great progress and become a focus in IBD study because they are non-invasive, convenient, and relatively inexpensive than are markers in biopsy tissue, stool, breath, and other body fluids. Aims: To review the available data on serological biomarkers for IBD. Methods: We searched PubMed using predefined key words on relevant literatures of serum biomarkers regarding diagnosis, evaluation of therapeutic efficacy, surveillance of disease activity, and assessment of prognosis for IBD. Results: We reviewed serological biomarkers that are well-established and widely used (e.g., C-reactive protein), newly discovered biomarkers (e.g., cytokines, antibodies, and non-coding RNAs), and also recently advancements in serological biomarkers (e.g., metabolomics and proteomics) that are used in different aspects of IBD management. Conclusions: With such a wealth of researches, to date, there are still no ideal serum biomarkers for IBD. Serum profiling and non-coding RNAs are just starting to blossom but reveal great promise for future clinical practice. Combining different biomarkers can be valuable in improving performance of disease evaluation.

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Inflammatory cytokines: from discoveries to therapies in IBD

Cited by 115 publications

References 134 publications

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

Serum Biomarkers for Inflammatory Bowel Disease

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