• 한국임상약학회지
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• 제28권4호
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• pp.333-341
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• 2018

Objective: Tumor necrosis factor-alpha (TNF-alpha) inhibitors are used as a treatment in various immune-mediated inflammatory diseases (IMIDs). Tuberculosis (TB) risk is reported in several meta-analyses in patients treated with TNF-alpha inhibitors. The purpose of this study is to collect, review, and evaluate the TB risk in TNF-alpha inhibitors according to IMIDs indications and between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors. Methods: A systematic literature search on systematic reviews and meta-analyses was performed in PubMed, MEDLINE, Cochrane library, and EMBASE. We identified meta-analyses that evaluated TB infection risk of TNF-alpha inhibitors in IMIDs patients. Results: Thirteen meta-analyses including 41 study results were included in this umbrella review. IMIDs patients treated with TNF-alpha inhibitors had an increased risk of TB than control group (placebo with or without standard therapy patients) (relative risk ratio (RR) 2.057, 95% confidence interval (CI) 1.697 to 2.495). Among them, RA patients with TNF-alpha inhibitors had a higher risk of TB than control group (RR 1.847, 95% CI 1.385 to 2.464), and non-RA patients with TNF-alpha inhibitors had an increased risk of TB (RR 2.236, 95% CI 1.284 to 3.894). In subgroup analysis on TB risk between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors in RA patients, the analysis indicated that monoclonal-antibody TNF-alpha inhibitors had higher risk of TB than soluble-receptor TNF-alpha inhibitor (RR 2.880, 95% CI 1.730 to 4.792). Conclusion: This umbrella review confirms that the risk of TB is significantly increased in TNF-alpha inhibitor treated patients compared to control group.

• The Korean Journal of Physiology and Pharmacology
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• 제15권2호
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• pp.115-122
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• 2011

The aim of this study was to investigate whether matrix metalloproteinase (MMP) inhibitors attenuate neuroinflammation in an ischemic brain following photothrombotic cortical ischemia in mice. Male C57BL/6 mice were anesthetized, and Rose Bengal was systemically administered. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold white light. MMP inhibitors, such as doxycycline, minocycline, and batimastat, significantly reduced the cerebral infarct size, and the expressions of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and indoleamine 2,3-dioxygenase (IDO). However, they had no effect on the expressions of heme oxygenase-1 and neuroglobin in the ischemic cortex. These results suggest that MMP inhibitors attenuate ischemic brain injury by decreasing the expression levels of MCP-1, TNF-${\alpha}$, and IDO, thereby providing a therapeutic benefit against cerebral ischemia.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.125.2-126
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• 2003

Human tumor necrosis factor-alpha (TNFa) is a key pro-inflammatory cytokine produced by activated monocytes and macrophage as a part of the self-defence machinery. TNF-a converting enzyme (TACE) is the metalloproteinase that processes the membrane bound precursor of TNFa to the soluble component. (omitted)

• 생명과학회지
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• 제16권7호
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• pp.1207-1213
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• 2006

Tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$는 염증성 골질환에서의 골조직의 손실과 밀접한 관련이 있다. 본 연구에서는 인체 골수 유래 중간엽 줄기세포의 골세포로의 분화과정에 대한 $TNF-{\alpha}$의 영향을 조사하였다. $TNF-{\alpha}$는 골수 유래 중간엽 줄기세포의 골세포로의 분화를 나타내는 표시인 세포외 무기질 축적과 alkaline phosphatase의 발현의 증가를 일으켰으며 2ng/ml의 농도에서 최대의 증가를 나타내었다. $TNF-{\alpha}$에 의한 골세포로의 분화는 $NF_kB$의 저해제에 의해서는 영향받지 않았으나 JNK 특이 저해제인 SP600125에 의해 완벽하게 억제되었다. 이는 $TNF-{\alpha}$에 의한 골수 유래 중간엽 줄기세포의 골세포로의 분화과정에 JNK가 중요한 역할을 한다는 것을 제시한다.

• 한국임상약학회지
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• 제25권4호
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• pp.246-253
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• 2015

Background & Object: Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes ankylosis and deformation of axial joints. Since current medicine cannot cure the disease yet, alleviating pain and preventing deformation with medications are the main therapy for patients with AS. The key medications for these purposes include nonsteroidal anti-inflammatory drugs (NSAIDs), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) inhibitors. This study aims to analyze prescribing patterns of AS patients in South Korea. Method: National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 was analyzed. Patients with AS were identified with Korean Standard Classification of Diseases code-6, which was M45. The rates of prescription, discontinuation, and switching ingredients were calculated for each medication during 2013. Results: Total number of patients was 655, and most of them were male (n = 514, 78.5%). Of all age groups, the proportion of 30-40 year old patients was the greatest (35.1%). The most utilized drug class was NSAIDs (82.4%). Less than half of patients were prescribed $TNF-{\alpha}$ inhibitors (n = 212, 32.4%). Meloxicam, aceclofenac, and celecoxib were the most frequently prescribed NSAIDs. In case of $TNF-{\alpha}$ inhibitors, adalimumab, etanercept and infliximab were the top three most prescribed drugs. Although not recommended by the current practice guideline, significant proportions of patients were identified using disease modifying anti-rheumatic drugs (DMARDs). Conclusion: Considering the current practice guideline and previous studies about the efficacy, the use of DMARDs should be reduced and medical insurance term in South Korea should be re-examined.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.135-143
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• 2018

Tumor necrosis $factor-{\alpha}$ ($TNF{\alpha}$) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which $TNF{\alpha}$-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS ($10{\mu}g/ml$) in the presence or absence of a type 1 TACE inhibitor ($1{\mu}M$) or type 2 TACE inhibitor ($10{\mu}M$). LPS treatment induced increased serum creatinine, $TNF{\alpha}$, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.

• Clinical Endoscopy
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• 제56권2호
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• pp.239-244
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• 2023

Tuberculosis is an adverse event in patients with Crohn's disease receiving anti-tumor necrosis factor (TNF) therapy. However, tuberculosis presenting as a bronchoesophageal fistula (BEF) is rare. We report a case of tuberculosis and BEF in a patient with Crohn's disease who received anti-TNF therapy. A 33-year-old Korean woman developed fever and cough 2 months after initiation of anti-TNF therapy. And the symptoms persisted for 1 months, so she visited the emergency room. Chest computed tomography was performed upon visiting the emergency room, which showed BEF with aspiration pneumonia. Esophagogastroduodenoscopy with biopsy and endobronchial ultrasound with transbronchial needle aspiration confirmed that the cause of BEF was tuberculosis. Anti-tuberculosis medications were administered, and esophageal stent insertion through endoscopy was performed to manage the BEF. However, the patient's condition did not improve; therefore, fistulectomy with primary closure was performed. After fistulectomy, the anastomosis site healing was delayed due to severe inflammation, a second esophageal stent and gastrostomy tube were inserted. Nine months after the diagnosis, the fistula disappeared without recurrence, and the esophageal stent and gastrostomy tube were removed.

• BMB Reports
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• 제32권2호
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• pp.140-146
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• 1999

When murine fibrosarcoma L929 cells, a TNF-sensitive cell line, were treated with recombinant human tumor necrosis factor-$\alpha$ (rhTNF-$\alpha$), the activities of glycolytic regulatory enzymes and lactate dehydrogenase increased up to 100-150% compared to the control L929 cells after TNF treatment. By using various metabolic inhibitors and activators, it was found that cAMP-dependent protein kinase is responsible for the increase of activities of the glycolytic enzymes. The activities of glycolytic regulatory enzymes and lactate dehydrogenase of TNF-resistant A549 cells, a human lung carcinoma cell line, did not increase significantly compared to TNF-sensitive L929 cells upon TNF treatment. In contrast, the pyruvate carboxylase activities of A549 cells, but not L929 cells, increased up to 30~40% after TNF treatment. The data suggest that pyruvate carboxylase activity may contribute to the compensation of energy loss mediated by TNF treatment in TNF-resistant A549 cells.

• The Korean journal of internal medicine
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• 제33권6호
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• pp.1241-1251
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• 2018

Background/Aims: To estimate the level of agreement and positivity rates of latent tuberculosis infection (LTBI) tests prior to the use of tumor necrosis factor (TNF) inhibitors in relation to underlying rheumatic diseases and endemic tuberculosis levels. Methods: The Ovid-Medline, Embase, and Cochrane Libraries were searched for articles before October 2013 involving LTBI screening in rheumatic patients, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and psoriatic arthritis. Results: In pooled analyses, 5,224 rheumatic patients had undergone both a tuberculin skin test (TST) and an interferon-gamma release assay (IGRA) before TNF inhibitors use. The positivity of TST, QuantiFERON-TB Gold In Tube (QFT-GIT), and T-SPOT.TB (T-SPOT) tests were estimated to be 29%, 17%, and 18%, respectively. The agreement percentage between the TST and QFT-GIT, and between the TST and T-SPOT were 73% and 75%. Populations from low-to-moderate endemic TB presented with slightly less agreement (71% between TST and QFT-GIT, and 74% between TST and T-SPOT) than patients from high endemic countries (73% between TST and QFT-GIT, and 81% between TST and T-SPOT). By underlying disease stratification, a lower level of agreement between TST and QFT-GIT was found among AS (64%) than among JIA (77%) and RA patients (73%). Conclusions: We reaffirm the current evidence for accuracy of LTBI test done by TST and IGRA among rheumatic patients is inconsistent. Our stratified analysis suggests different screening strategies might be needed in clinical settings considering the endemic status in the patient's country of origin and the precise nature of underlying diseases.

• 생명과학회지
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• 제29권11호
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• pp.1251-1257
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• 2019

본 연구에서는 펩티도글리칸이 단핵세포의 $TNF-{\alpha}$ 발현에 미치는 영향을 조사하였고, 또한 펩티도글리칸에 의한 $TNF-{\alpha}$ 발현에 관련된 세포의 요소들을 연구하였다. 사람의 단핵세포주인 THP-1 세포를 펩티도글리칸에 노출시키는 경우 $TNF-{\alpha}$ 분비 증가뿐만 아니라 $TNF-{\alpha}$ 유전자 전사를 유도하는 결과를 가져왔다. TLR-2/4의 억제제인 OxPAPC은 펩티도글리칸에 의한 $TNF-{\alpha}$의 발현을 저해하였다. 그리고 U0126, SB202190, SP6001250, LY294002, Akti IV, rapamycin, NAC, DPI 같은 약리학적 저해제 또한 $TNF-{\alpha}$ 발현을 유전자/단백질 수준에서 상당히 약화시켰다. 그러나 polymyxin B는 $TNF-{\alpha}$ 발현에 영향을 주지않았다. 따라서 펩티도글리칸이 TLR-2, PI3K, Akt, mTOR, MAPKs, ROS 등을 통하여 단핵세포의 $TNF-{\alpha}$ 발현을 증가시킴을 확인하였다.