The Therapeutic Role of Interleukin-1 Inhibition in Idiopathic Recurrent Pericarditis: Current Evidence and Future Challenges

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.

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Role of Toll Interleukin-1 Receptor (IL-1R) 8, a Negative Regulator of IL-1R/Toll-Like Receptor Signaling, in Resistance to Acute Pseudomonas aeruginosa Lung Infection

Infection and Immunity ◽

10.1128/iai.05695-11 ◽

2011 ◽

Vol 80 (1) ◽

pp. 100-109 ◽

Cited By ~ 30

Author(s):

Tania Véliz Rodriguez ◽

Federica Moalli ◽

Nadia Polentarutti ◽

Moira Paroni ◽

Eduardo Bonavita ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Interleukin 1 ◽

Bacterial Load ◽

Lung Infection ◽

Negative Regulator ◽

Current Evidence ◽

Toll Like Receptor ◽

Content Type ◽

Deficient Mice

ABSTRACTToll interleukin-1 receptor (IL-1R) 8 (TIR8), also known as single Ig IL-1 receptor (IL-R)-related molecule, or SIGIRR, is a member of the IL-1R-like family, primarily expressed by epithelial cells. Current evidence suggests that TIR8 plays a nonredundant role as a negative regulatorin vivounder different inflammatory conditions that are dependent on IL-R and Toll-like receptor (TLR) activation. In the present study, we examined the role of TIR8 in innate resistance to acute lung infections caused byPseudomonas aeruginosa, a Gram-negative pathogen responsible for life-threatening infections in immunocompromised individuals and cystic fibrosis patients. We show that Tir8 deficiency in mice was associated with increased susceptibility to acuteP. aeruginosainfection, in terms of mortality and bacterial load, and to exacerbated local and systemic production of proinflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], IL-1β, and IL-6) and chemokines (CXCL1, CXCL2, and CCL2). It has been reported that host defense againstP. aeruginosaacute lung infection can be improved by blocking IL-1 since exaggerated IL-1β production may be harmful for the host in this infection. In agreement with these data, IL-1RI deficiency rescues the phenotype observed in Tir8-deficient mice: in Tir8−/−IL-1RI−/−double knockout mice we observed higher survival rates, enhanced bacterial clearance, and reduced levels of local and systemic cytokine and chemokine levels than in Tir8-deficient mice. These results suggest that TIR8 has a nonredundant effect in modulating the inflammation caused byP. aeruginosa, in particular, by negatively regulating IL-1RI signaling, which plays a major role in the pathogenesis of this infectious disease.

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Functional characterization and therapeutic role of interleukin-1 receptor-associated kinase 1 (IRAK1) in hepatocellular carcinoma

10.5353/th_991043979528603414 ◽

2016 ◽

Author(s):

Yik-ling, Bowie Cheng

Keyword(s):

Hepatocellular Carcinoma ◽

Interleukin 1 ◽

Functional Characterization ◽

Therapeutic Role

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Emerging Therapies for Recurrent Pericarditis: Interleukin‐1 inhibitors

Journal of the American Heart Association ◽

10.1161/jaha.121.021685 ◽

2021 ◽

Vol 10 (19) ◽

Author(s):

Saberio Lo Presti ◽

Tarec K. Elajami ◽

Reza Reyaldeen ◽

Chris Anthony ◽

Massimo Imazio ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Interleukin 1 ◽

Poor Quality ◽

Adverse Outcomes ◽

Current Evidence ◽

First Episode ◽

Inflammatory Disorder ◽

Recurrent Pericarditis ◽

Acute Pericarditis ◽

Beneficial Impact

Abstract Recurrent pericarditis (RP) is a complex inflammatory disorder associated with adverse outcomes and poor quality of life. After the first episode of acute pericarditis, a non‐negligible group of patients will fail to achieve complete remission despite treatment and will be challenged by side effects from the chronic use of medications like corticosteroids. The cause of RP remains unknown in the majority of cases, mainly due to a gap in knowledge of its complex pathophysiology. Over the past 2 decades, the interleukin‐1 (IL‐1) pathway has been uncovered as a key element in the inflammatory cascade, allowing the development of pharmacological targets known as IL‐1 inhibitors. This group of medications has emerged as a treatment option for patients with RP colchicine‐resistance and steroid dependents. Currently, anakinra and rilonacept, have demonstrated beneficial impact in clinical outcomes with a reasonable safety profile in randomized clinical trials. There is still paucity of data regarding the use of canakinumab in the treatment of patients with RP. Although further studies are needed to refine therapeutic protocols and taper of concomitant therapies, IL‐1 inhibitors, continue to consolidate as part of the pharmacological armamentarium to manage this complex condition with potential use as monotherapy. The aim of this review is to highlight the role of IL‐1 pathway in RP and discuss the efficacy, safety, and clinical applicability of IL‐1 inhibitors in the treatment of RP based on current evidence.

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