Safety of Anti-Tumor Necrosis Factor Therapies in Arthritis Patients

Nanau, Radu M.; Neuman, Manuela G.

doi:10.18433/j3wp4f

Cited by 41 publications

(32 citation statements)

References 237 publications

(237 reference statements)

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“…Biologics based on anti-TNFα antibodies are widely used in humans for the treatment of autoimmune diseases and can lead to increased susceptibility to disease or reactivation of latent infections (Saraceno and Chimenti 2008; Mootoo et al. 2009; Nanau and Neuman 2014; Shi and Liu 2014). …”

Section: Introductionmentioning

confidence: 99%

Effect of in vivo neutralisation of Tumor Necrosis Factor alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections

Rossi¹,

Grant²,

Mastroeni³

2017

Pathogens and Disease

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Immunity can co-operate with antibiotics, but can also antagonize drug efficacy by segregating the bacteria to areas of the body that are less accessible to antimicrobials, and by selecting for subpopulations with low division rates that are often difficult to eradicate. We studied the effect of an anti-inflammatory/immunosuppressive anti-TNFα treatment, which accelerates bacterial growth in the tissues and inhibits or reverses the formation of granulomas, on the efficacy of ampicillin and ciprofloxacin during a systemic Salmonella enterica infection of the mouse. The anti-TNFα treatment neither precluded nor enhanced the efficacy of antibiotic treatment. However, the anti-TNFα treatment rendered the animals susceptible to the rapid relapse of the infection seen after cessation of the antibiotic treatment. Reactivation of an established infection, due to late administration of anti-TNFα antibodies, could be successfully controlled by antibiotics, but full clearance of the bacterial load from the tissues was not achieved. We conclude that the lack of TNFα does not preclude the efficacy of antibiotic treatment and must be monitored with care due to post-treatment relapses. Combinations of anti-cytokine compounds and antibiotic molecules may not be the best way to treat persistent infections with intracellular bacteria like Salmonella.

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Section: Introductionmentioning

confidence: 99%

Effect of in vivo neutralisation of Tumor Necrosis Factor alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections

Rossi¹,

Grant²,

Mastroeni³

2017

Pathogens and Disease

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“…On the other hand, IL-1␤ blockade shows greater promise (18,19). However, IL-1␤ blockade using monoclonal antibodies is likely to suffer from immunosuppressive side effects observed with TNF blockers (23). Thus, other anti-inflammatory approaches should be investigated.…”

mentioning

confidence: 99%

θ-Defensin RTD-1 improves insulin action and normalizes plasma glucose and FFA levels in diet-induced obese rats

Tran

Buchanan

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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-Defensin RTD-1 improves insulin action and normalizes plasma glucose and FFA levels in diet-induced obese rats. Am J Physiol Endocrinol Metab 309: E154 -E160, 2015. First published May 19, 2015 doi:10.1152/ajpendo.00131.2015.-Inflammation is implicated in metabolic abnormalities in obesity and type 2 diabetes. Because -defensins have anti-inflammatory activities, we tested whether RTD-1, a -defensin, improves metabolic conditions in diet-induced obesity (DIO). DIO was induced by high-fat feeding in obese-prone CD rats from 4 wk of age. Starting at age 10 wk, the DIO rats were treated with saline or RTD-1 for 4 or 8 wk. DIO rats gained more weight than low-fat-fed controls. RTD-1 treatment did not alter body weight or calorie intake in DIO rats. Plasma glucose, FFA, triglyceride (TG), and insulin levels increased in DIO rats; RTD-1 normalized plasma glucose and FFA levels and showed tendencies to lower plasma insulin and TG levels. Hepatic and skeletal muscle TG contents increased in DIO rats; RTD-1 decreased muscle, but not hepatic, TG content. Insulin sensitivity, estimated using homeostasis model assessment of insulin resistance and the glucose clamp technique, decreased in DIO rats, but this change was markedly reversed by RTD-1. RTD-1 had no significant effects on plasma cytokine/ chemokine levels or IL-1␤ and TNF-␣ expression in liver or adipose tissues. RTD-1 treatment decreased hepatic expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, suggesting that the effect of RTD-1 on plasma glucose (or insulin action) might be mediated by its effect to decrease hepatic gluconeogenesis. Thus, RTD-1 ameliorated insulin resistance and normalized plasma glucose and FFA levels in DIO rats, supporting the potential of RTD-1 as a novel therapeutic agent for insulin resistance, metabolic syndrome, or type 2 diabetes.high-fat feeding; inflammation; insulin resistance; type 2 diabetes; gluconeogenesis -DEFENSINS ARE NATURALLY OCCURRING, cyclic octadecapeptides expressed in Old World monkeys but not in great apes or humans (26,30,31). They are the only known class of cyclic peptides of animal origin (5). Selsted et al. (34) have shown that -defensins have potent anti-inflammatory effects in vitro and in vivo, in contrast to proinflammatory and immuneactivating properties of mammalian ␣-and ␤-defensins, genetically related to -defensins (1, 11). The macrocyclic conformation of -defensins confers remarkable stability in vivo and in vitro (5). Preclinical studies have shown the peptides to be nontoxic, nonimmunogenic, and nonimmunosuppressive at doses that inhibit inflammation in vivo (25), providing strong support for their potential as anti-inflammatory therapeutics. Although the details of the mode of action are still being investigated, it is evident that the lead molecule rhesus -defensin 1 (RTD-1) suppresses Toll-like receptor (TLR)-mediated secretion of several pro-inflammatory cytokines, including TNF-␣, IL-1␤, and IL-6 (25).Circulating levels of proinflammatory cytokines are increased in obesi...

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“…A recently published systematic review about the safety of anti-TNF treatment in patients with rheumatoid arthritis showed that infections, particularly reactivation of latent tuberculosis or de novo tuberculosis, infusion reactions and abnormalities in hepatic liver enzymes are the most common side effects in patients treated with infliximab [53]. The main adverse effects of adalimumab were infections and infusion reactions.…”

Section: What Side Effects Have Been Described For Tnf Antagonists Used?mentioning

confidence: 99%

Paradoxical Inflammation in IBD Patients Treated with Anti-Tumor Necrosis Factor Alpha Therapy

Niess¹

2017

Austin J Gastroenterol

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The development of tumor necrosis factor (TNF) antagonists has revolutionized the treatment of inflammatory bowel disease (IBD). Paradoxically, TNF antagonists can also induce inflammation, such as psoriasis induced by TNF antagonists. The mechanisms by which TNF antagonists induce paradoxical inflammation, has remained largely unresolved. In this review we will focus on the immunologic effects of the therapy with TNF antagonists and give an overview of TNF antagonist-induced immunologically mediated diseases.

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Safety of Anti-Tumor Necrosis Factor Therapies in Arthritis Patients

Cited by 41 publications

References 237 publications

Effect of in vivo neutralisation of Tumor Necrosis Factor alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections

Effect of in vivo neutralisation of Tumor Necrosis Factor alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections

θ-Defensin RTD-1 improves insulin action and normalizes plasma glucose and FFA levels in diet-induced obese rats

Paradoxical Inflammation in IBD Patients Treated with Anti-Tumor Necrosis Factor Alpha Therapy

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