Pentoxifylline in patients with ulcerative colitis treated with mesalamine by modulation of IL-6/STAT3, ZO-1, and S1P pathways: a randomized controlled double-blinded study.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2024-10-01 Epub Date: 2024-08-27 DOI:10.1007/s10787-024-01560-6

Mostafa M Bahaa, Sahar K Hegazy, Maha M Maher, Monir M Bahgat, Sahar M El-Haggar

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Abstract

Background: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that lasts a long time and has a variety of causes.

Aim: The primary aim of this study was to evaluate pentoxifylline's (PTX) essential function in patients with UC.

Methods: Fifty-two mild to moderate UC patients who matched the eligibility requirements participated in this clinical study. One gram of mesalamine (t.i.d.) and a placebo were administered to the mesalamine group (n = 26) for a duration of 24 weeks. Mesalamine 1 g t.i.d. and PTX 400 mg two times daily were administered to the PTX group (n = 26) for 24 weeks. A gastroenterologist investigated patients at the start and 6 months after the medication was given to assess disease activity index (DAI) and numeric pain rating scale (NRS). Also, interleukin-6 (IL-6), sphingosine 1 phosphate (S1P), tumor necrosis factor-alpha (TNF-α), and fecal myeloperoxidase (MPO) were measured before and after therapy. Zonula occuldin-1 (ZO-1) and signal transducer and activator of transcription factor-3 (STAT-3) expression was assessed before and after therapy as well as histological assessment. Short Form 36 Health Survey (SF-36), was assessed for each patient before and after 6 months of treatment.

Results: The PTX group showed statistically lower levels of serum SIP, TNF-α, IL-6, faecal MPO, gene expression of STAT-3, and a significant increase of ZO-1 in comparison with the mesalamine group. DAI and NRS significantly decreased whereas SF-36 significantly increased in the PTX group.

Conclusion: PTX could alleviate inflammation in patients with UC, so it might be promising adjunctive for patients with UC.

Trial registration identifier: NCT05558761.

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通过调节 IL-6/STAT3、ZO-1 和 S1P 通路对接受美沙拉秦治疗的溃疡性结肠炎患者进行五氯硝基苯胺治疗：一项随机对照双盲研究。

背景：溃疡性结肠炎（UC）是一种病程长、病因多的炎症性肠病（IBD）。目的：本研究的主要目的是评估喷托非韦林（PTX）在UC患者中的基本功能：52名符合条件的轻中度UC患者参与了这项临床研究。美沙拉明组（26 人）服用 1 克美沙拉明（t.i.d.）和安慰剂，疗程为 24 周。PTX组（26人）服用1克美沙拉明（t.i.d.）和400毫克PTX，每日2次，疗程24周。胃肠病学家在开始用药时和用药 6 个月后对患者进行了调查，以评估疾病活动指数（DAI）和数字疼痛评分量表（NRS）。此外，治疗前后还测量了白细胞介素-6（IL-6）、磷酸鞘磷脂 1（S1P）、肿瘤坏死因子-α（TNF-α）和粪便髓过氧化物酶（MPO）。对治疗前后的Zonula occuldin-1 (ZO-1)和信号转导及激活转录因子-3 (STAT-3)的表达进行了评估，并进行了组织学评估。在治疗前后 6 个月，对每位患者进行了简表 36 健康调查（SF-36）：结果：与美沙拉秦组相比，PTX 组的血清 SIP、TNF-α、IL-6、粪便 MPO、STAT-3 基因表达水平显著降低，而 ZO-1 则显著升高。PTX组的DAI和NRS明显下降，而SF-36明显上升：结论：PTX可减轻UC患者的炎症反应，因此对UC患者来说可能是一种很有前景的辅助治疗药物：NCT05558761。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]