Problems encountered during anti-tumour necrosis factor therapy

Desai, Sheetal; Fürst, Daniel E.

doi:10.1016/j.berh.2006.06.002

Cited by 203 publications

(164 citation statements)

References 123 publications

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“…Overproduction of TNF-a believes to play a key role in the onset and progression of various pathologies such as disseminated intravascular coagulation and death in septic choc and cerebral malaria (Medana et al 1997;Murphy et al 1998) and a range of inflammatory diseases including asthma (Bj€ ornsdottir & Cypcar 1999), dermatitis, inflammatory bowel disease, cystic fibrosis, rheumatoid arthritis and multiples sclerosis (Sekut & Connolly 1996); in addition, TNF-a has been shown to be a crucial mediator of NSAIDs-induced gastric mucosal injury (Santucci et al 1994). In spite of enormous efforts, the only available drugs to inhibit TNFa activity, in clinics, are proteins (Etanercept, Infliximab, Adalimumab and Anakinra) that display adverse effects such as aplastic anaemia, pancytopenia, vasculitis, demyelination and congestive heart failure (Desai & Furst 2006). Therefore, there is a continuing interest in the search of potent anti-inflammatory natural products that can block TNF-a signalling without side effects.…”

Section: Introductionmentioning

confidence: 99%

In vitroimmunomodulatory activity andin vivoanti-inflammatory and analgesic potential with gastroprotective effect of the Mediterranean red algaLaurencia obtusa

Lajili

Deghrigue

Amor

et al. 2016

Pharmaceutical Biology

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Context: Red algae have been recognized as a rich natural source of compounds possessing interesting biological and pharmacological activities. Objective: This work investigates anti-inflammatory, analgesic and gastroprotective activities of MeOH/ CH 2 Cl 2 crude extract and its fractions F1 (50% MeOH) and F2 (80% MeOH) from the whole alga plant Laurencia obtusa Hudson (Rhodomelaceae). Materials and methods: Anti-inflammatory activity was evaluated in vitro using cytometric bead array (CBA) technology to follow up the secretion of tumour necrosis factor alpha (TNF-a) in lipopolysaccharide activated THP-1 monocytic cells at doses of 10-250 lg/mL and in vivo using carrageenan-induced paw oedema in Wistar rats at doses of 25, 50, 100 and 200 mg/kg. Crude extract and fractions were tested at the doses of 25, 50, 100 and 200 mg/kg for peripheral and central analgesic activity by acetic acid-induced writhing test and hot-plate method, respectively, in Swiss albino mice. Gastroprotective activity was evaluated using HCl/ethanol-induced gastric ulcer test in rats at doses of 25, 50, 100 and 200 mg/kg. Results: Crude extract, F1 and F2 showed an interesting inhibition of TNF-a secretion with IC 50 values of 25, 52 and 24 lg/mL, respectively, and a significant anti-inflammatory activity in vivo (p < 0.01), 3 h after carrageenan injection, the oedema inhibition was 55.37%, 52.18% and 62.86%, respectively, at the dose of 100 mg/kg. Furthermore, they showed a significant peripheral analgesic activity with 53.79%, 55.92% and 57.37% (p < 0.01) of writhing inhibition, respectively. However, no significant activity was found in the hotplate test. An interesting gastroprotective effect was observed with crude extract and its fractions F1 and F2 with a gastric ulcer inhibition of 65.48%, 77.42% and 81.29%, respectively, at the dose of 50 mg/kg. Discussion and conclusion: These results suggest that L. obtusa might be used as a potential source of natural anti-inflammatory and analgesic agents with gastroprotective effect. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

In vitroimmunomodulatory activity andin vivoanti-inflammatory and analgesic potential with gastroprotective effect of the Mediterranean red algaLaurencia obtusa

Lajili

Deghrigue

Amor

et al. 2016

Pharmaceutical Biology

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“…74 ‹sveç çal›flma grubunun RA hastalar›nda TNF antagonistlerinin solid kanser geliflim üze-rine etkilerini inceledikleri çal›flmalar›nda genel olarak riskin artmad›¤›n› göstermifltir. Hatta yazarlar bu serideki bayan hastalar›nda meme kanseri riskinin bu tedavi ile anlaml› derecede azald›¤›n› bildirmifllerdir.…”

Section: Tnf Antagonistleriunclassified

“…Bu çal›flmada ciddi enfeksiyon kriteri olarak; hastalar›n hospitalizasyonu, intravenöz antibiyotik kullan›m› ve ölüm geliflimi kabul edildi¤inde etanersept, infliksimab ve adalimumab'›n klasik tedavilere göre riski artt›rmad›klar› bulunmufltur. 74 Benzer flekilde Burmester ve ark. 6610 RA hastada adalimumab'›n etkisini inceledikleri prospektif araflt›rmalar›nda ileri yafl, erkek cinsiyet, efllik eden kardiak veya pulmoner hastal›klar ve ileri RA aktivitesinin ciddi enfeksiyon için en önemli risk faktörleri oldu¤unu ortaya koymufltur.…”

Section: Tnf Antagonistleriunclassified

“…Hayvan çal›flmalar› yük-sek TNF-α düzeylerinin sol ventriküler yetmezli¤ine ve sol kalp yetmezli¤ine neden oldu¤unu göstermifltir. 74 TNF-alfa blokörlerinin en yayg›n kullan›ld›¤› hastal›k grubu olan RA'te çeflitli hastal›klar yan›nda kardiovasküler morbidite ve mortalitenin de artt›¤› bilinmektedir. Bu durumun sistemik inflamasyon ile birlikte artm›fl ateroskleroz, miyokardial enfarktüs, kalp yetmezli¤i ve serebrovasküler hastal›klar ile iliflkili oldu¤u düflünülmek-tedir.…”

Section: Tnf Antagonistleriunclassified

“…123 TNF antagonistleri ile nadir de olsa görülen klinik tablolardan biri MS, optik nörit, ensefalit vb gibi demyelinizan hastal›klard›r. 74 Mohan ve ark. anti-TNF ajan kullan›m›na ba¤l› bildirdikleri 20 demyelinizasyon vakas›-n›n 18'inde etanersept, 2'sinde ise infliksimab kullan›-m›na sekonder geliflti¤ini bildirmifllerdir.…”

Section: Tnf Antagonistleriunclassified

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New Treatment Alternatives in the Management of Non-İnfectious İntraocular İnflammations: Biologic Agents

Emre¹,

Tutkun²

2011

tjo

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ÖzetEnfeksiyöz olmayan üveitlerin tedavisinde son y›llara kadar genel olarak immün sistemi bask›layan ilaçlar kullan›lmak-tayd›. Ancak gen mühendisli¤indeki geliflmeler, inflamatuar süreçte yer alan özgün molekülleri hedefleyen proteinlerin sentezini ve bu proteinlerin terapötik olarak kullan›lmalar›n› mümkün k›lm›flt›r. Genel olarak protein yap›s›ndaki bu ajanlar biyolojik ajanlar olarak adland›r›lm›fllard›r. Oftalmologlar›n biyolojik ajanlar ile tecrübeleri s›n›rl› olsa da, bu ajanlar romatoloji ve dermatoloji baflta olmak üzere di¤er disiplinler taraf›ndan yo¤un biçimde kullan›lmaktad›rlar. ‹nterferon, infliksimab ve adalimumab baflta olmak üzere birçok biyolojik ajan›n üveit hastalar›nda kullan›m› ile ilgili literatür verisi olmas›na ra¤men henüz bu endikasyonda ruhsatl› kullan›mlar› yoktur. Ayr›ca bu ajanlar›n kullan›m› s›ras›nda dikkat edilmesi gereken güvenlik önlemleri ve önemli risk faktörleri mevcuttur. Bu derlemenin amac›, dirençli üveit hastalar›nda kullan›labilen biyolojik ajanlar konusunda güncel ve kapsaml› bilgi sunmakt›r. ( SummaryConventional immunosuppressive agents have been traditionally used for the treatment of noninfectious uveitis. Recent developments in genetic engineering have made it possible to synthesize proteins that target specific molecules playing role in the inflammatory response. These agents are generally in protein structure and are named biologic agents. While there is limited experience with biologics in the field of ophthalmology, they are commonly used in other disciplines such as rheumatology and dermatology. Although considerable data have accumulated in the uveitis literature regarding the use of biologic agents, including mainly interferon, infliximab, and adalimumab, their use for this indication is still off-label. Moreover, there are certain precautions that have to be taken into account, as well as important safety issues associated with their use. The purpose of this paper is to present an updated comprehensive review of biologic agents that may be used for the treatment of refractory uveitis. (Turk J Ophthalmol 2011; 41: 243-55 GiriflEnfeksiyöz olmayan üveitlerin tedavisinde kullan›lmakta olan immunsupresan ajanlar, ba¤›fl›kl›k sistemini genel olarak bask›lamakta veya sapt›rmaktad›rlar. Bu tedavi yöntem-lerinin sebep olduklar› ciddi yan etkiler ile tedaviye dirençli olgular, hekimleri yeni tedavi aray›fllar›na itmektedir. Son y›llarda araflt›r›lan biyolojik ajanlar, inflamatuar süreçteki öz-gün molekülleri (proteinleri) etkileyerek ba¤›fl›kl›k sisteminde daha s›n›rl› ancak etkin bir tedavi sa¤lamaktad›rlar. Biyolojik ajanlar, moleküler rekombinant DNA teknolojisi kullan›larak elde edilen proteinlerdir. Bu ajanlar›n büyük ço¤un-lu¤u monoklonal antikorlard›r. fiu an için enfeksiyöz olmayan üveitlerin tedavisinde bafll›ca kullan›lan biyolojik ajanlar 3 grupta s›n›fland›r›labilir; i. Interferon-α, ii. TNF-α antagonistleri ve iii. Çeflitli sitokin veya yüzey membran proteini gibi farkl› hedeflere yönelik antikorlar veya füzyon proteinleri.

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