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Nitric Oxide, Neutrophil/Lymphocyte, and Platelet/Lymphocyte Ratios as Promising Inflammatory Biomarkers in Complicated Crohn’s Disease: Outcomes of Corticosteroids and Anti-TNF-α Therapies

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Abstract

Crohn’s disease (CD) is a relapsing–remitting inflammatory bowel disease with a progressive course. The aim of our study was to evaluate the relationship between nitric oxide (NO), pro-inflammatory cytokines, and blood count-based ratios in patients with complicated Crohn’s disease as well as the outcome of corticosteroid or anti-TNF-α therapy. In this context, we evaluated the NLR as the ratio of neutrophils count to lymphocytes count, PLR as the ratio of platelets count to lymphocytes count, and MLR as the ratio of monocytes count to lymphocytes count in patients and controls. Furthermore, we assessed NO production by the Griess method in plasma along with iNOS and NF-κB expression by immunofluorescence method in intestinal tissues of patients and controls. In the same way, we evaluated plasma TNF-α, IL-17A, and IL-10 levels using ELISA. Our results indicate that blood count-based ratios NLR, PLR, and MLR were significantly higher in patients compared to controls. In addition, increased systemic levels of NO, TNF-α, and IL-17A and colonic expression of iNOS and NF-κB were observed in the same patients. Interestingly, the high ratio of NLR and MLR as well as NO production were significantly decreased in treated patients. Collectively, our findings suggest that nitric oxide as well as the blood count-based ratios (NLR, PLR, MLR) could constitute useful biomarkers in complicated Crohn’s disease, predicting the response to treatments.

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ACKNOWLEDGEMENTS

The authors acknowledge the technical staff of the General Surgery Department (Djilali Belkhenchir Hospital, Algiers, Algeria) and Anatomic Pathology Department (Nefissa Hamoud Hospital, Algiers, Algeria), the national agency of research development in health (ATRSS) which supported their project. The authors are grateful to participating patients and controls.

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All authors contributed to the study conception and design. Conceptualization: Imene Soufli, Chafia Touil-Boukoffa, and Nassim SidIdriss. Methodology: Imene Soufli, Abdelkrim Hablal, Samia Bessad, Moussa Labsi, Rania Sihem Boussa, and Fahima Ameur. Formal analysis and investigation: Imene Soufli, Manel Amri, Samia Bessad, Houda Belguendouz, and Sonia Ait Younes. Writing—original draft preparation: Imene Soufli. Writing—review and editing: Imene Soufli, Chafia Touil-Boukoffa, and Manel Amri. Supervision: Chafia Touil-Boukoffa and Nassim SidIdriss.

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Correspondence to Chafia Touil-Boukoffa.

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The local ethics committee of the “Algerian National Agency for Research in Health Sciences, ATRSS ex-ANDRS” in compliance with Helsinki Declaration has approved our study. All participants (patients and controls) included in this study provided their informed consent.

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Soufli, I., Hablal, A., Bessaad, S. et al. Nitric Oxide, Neutrophil/Lymphocyte, and Platelet/Lymphocyte Ratios as Promising Inflammatory Biomarkers in Complicated Crohn’s Disease: Outcomes of Corticosteroids and Anti-TNF-α Therapies. Inflammation 46, 1091–1105 (2023). https://doi.org/10.1007/s10753-023-01796-4

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