Research progress of interleukin-1 and its receptor antagonist Anakinra in Kawasaki disease / 中华实用儿科临床杂志

Kawasaki disease (KD) is an acute vasculitis that often occurs in children under 5 years of age, leading to coronary artery aneurysms.It is the leading cause of acquired heart disease in children in many countries.Coronary artery stenosis, thrombosis, and even myocardial infarction may occur in the long-term course of KD, which seriously threaten the health of children.The etiology and pathogenesis of KD are complex, and it is recognized that KD is caused by the interaction of multiple factors like the heredity, immunity, inflammation, and environmental factors.Interleukin-1 plays an important role in the occurrence and progression of KD.This study mainly reviews the research progress of interleukin-1 and its receptor antagonist Anakinra in KD.

The Effect of Anakinra on Acrylamide-induced Peripheral Neuropathy and Neuropathic Pain in Rats

Abstract Acrylamide is a neurotoxic compound. Moreover, anakinra is an interleukin-1 (IL-1) receptor antagonist used in rheumatoid arthritis treatment. This study investigated the effect of anakinra on acrylamide-related neuropathy and neuropathic pain. Acrylamide exposure caused a significant decrease in the pain threshold; an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) levels; and a decrease in total glutathione (tGSH) values in the sciatic nerve. This indicates hyperalgesia presence, oxidative stress, and peripheral nerve tissue inflammation. Anakinra treatment significantly reduced the MDA, IL-1ß, and TNF-α levels, and increased the pain threshold and mean tGSH values. The analgesic effect of anakinra was 67.9% at the first hour, increasing to 74.9% and 76.7% at the second and third hours, respectively. The group receiving acrylamide exhibited histopathological changes (e.g., swollen and degenerated axons, hypertrophic and hyperplasic Schwann cells, and congested vessels). The use of anakinra significantly improved these morphological changes. Anakinra is concluded to reduce neuropathic pain and prevent neurotoxic effect of acrylamide on peripheral nerves due to its analgesic, antioxidant, and anti-inflammatory properties

Uso de antirreumáticos en covid-19 desde la hidroxicloroquina hasta la anakinra pasando por tocilizumab y baricitinib: Una revisión de la literatura / Use of antirheumatic drugs in covid-19 from hydroxychloroquine to anakinra through tocilizumab and baricitinib: A review of the literature

Actualmente nos encontramos en una pandemia mundial causada por el coronavirus 2019 o COVID­19, presentando diferentes desafíos para el sistema de salud debido a que no se cuenta aún con alguna vacuna ni con un tratamiento que haya demostrado su eficacia en totalidad, siendo el manejo actual preventivo y de soporte. Por lo que, en esta revisión se estudiará a los fármacos antirreumáticos más resaltantes que tengan un probable efecto farmacológico, como son la hidroxicloroquina, el tocilizumab, el anakinra y el baricitinib, frente al COVID­19. Se espera que brinde apoyo para futuros tratamientos e investigaciones sobre la enfermedad.

We are currently in a global pandemic caused by the coronavirus 2019 or COVID-19, presenting different challenges for the health system due to the fact that there is still no vaccine or a treatment that has proven its effectiveness in its entirety, being the management current preventive and supportive. Therefore, this review will study the most prominent antirheumatic drugs that have a probable pharmacological effect, such as hydroxychloroquine, tocilizumab, anakinra and baricitinib, against COVID-19. It is expected that they will provide support for future treatments. and research on the disease

Uso de antirreumáticos en covid-19 desde la hidroxicloroquina hasta la anakinra pasando por tocilizumab y baricitinib: Una revisión de la literatura / Use of antirheumatic drugs in covid-19 from hydroxychloroquine to anakinra through tocilizumab and baricitinib: A review of the literature

RESUMEN Actualmente nos encontramos en una pandemia mundial causada por el coronavirus 2019 o COVID-19, presentando diferentes desafíos para el sistema de salud debido a que no se cuenta aún con alguna vacuna ni con un tratamiento que haya demostrado su eficacia en totalidad, siendo el manejo actual preventivo y de soporte. Por lo que, en esta revisión se estudiará a los fármacos antirreumáticos más resaltantes que tengan un probable efecto farmacológico, como son la hidroxicloroquina, el tocilizumab, el anakinra y el baricitinib, frente al COVID-19. Se espera que brinde apoyo para futuros tratamientos e investigaciones sobre la enfermedad.

ABSTRACT We are currently in a global pandemic caused by the coronavirus 2019 or COVID- 19, presenting different challenges for the health system due to the fact that there is still no vaccine or a treatment that has proven its effectiveness in its entirety, being the management current preventive and supportive. Therefore, this review will study the most prominent antirheumatic drugs that have a probable pharmacological effect, such as hydroxychloroquine, tocilizumab, anakinra and baricitinib, against COVID-19. It is expected that they will provide support for future treatments. and research on the disease.

Assessment of effectiveness of anakinra and canakinumab in patients with colchicine-resistant/unresponsive familial Mediterranean fever

Abstract İntroduction: Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation. Anti-interleukin-1 (Anti-IL-1) treatments are recommended in colchicine resistant and/or intolerant FMF patients. This study aims to evaluate the efficacy of anakinra and canakinumab in FMF patients that are resistant/intolareted to colchicine or complicated with amyloidosis. Methods: Between January 2014 and March 2019, 65 patients following-up at Sivas Cumhuriyet University (Medical Faculty Rheumatology-Internal Medicine Department) who were diagnosed with FMF according to the criteria of Tel-Hashomer were included in the study. The laboratory values and clinical features of patients and disease activities were recorded at least every 3 months, and these data were analyzed. Results: Forty-one (63.1%) patients used anakinra (100 mg/day) and 24 (36.9%) patients used canakinumab (150 mg/8 week). The median duration of anti-IL-1 agents use was 7 months (range, 3-30). Fifteen (23.1%) cases were complicated with amyloidosis. Seven (10.8%) patients had renal transplantation. Overall, the FMF 50 score response was 96.9%. In the group that had a glomerular filtration rate (GFR) ≥ 60 ml/min/m2, the median proteinuria decreased from 2390 mg/day (range, 1400-7200) to 890 mg/day (range, 120-2750) (p = 0.008). No serious infections were detected, except in one patient. Conclusions: Anti-IL-1 agents are effective and safe in the treatment of FMF patients. These agents are particularly effective at reducing proteinuria in patients with GFR ≥ 60 ml/min/m2, but less effective in cases with FMF associated with arthritis and sacroiliitis. Large and long follow-up studies are now needed to establish the long-term effects of these treatments.

Bloqueio do receptor da interleucina-1 com anakinra inibe a cistite hemorrágica induzida por ifosfamida

Cistite hemorrágica (CH) induzida por ifosfamida (IFO) é uma importante complicação clínica em pacientes com câncer. Atualmente, mesna e hiper-hidratação são utilizadas como profilaxia, a despeito de ainda ser observada CH através de cistoscopia e histopatologia mesmo com essas medidas. A participação de interleucina-1 (IL-1) e fator de necrose tumoral (TNF) na patogênese da CH provê alvos para o tratamento dessa doença. Assim, esse trabalho objetivou avaliar o efeito protetor do antagonista do receptor da IL-1 (anakinra) e do anticorpo anti-TNF-alfa (infliximabe) nas respostas inflamatórias, nociceptivas e funcionais da CH experimental induzida por IFO em camundongos. Foram utilizados camundongos Swiss, C57BL6, IL-1R-/-, CASP1-/-, TNFR1-/-, TNFR1/R2-/-. Os animais WT foram submetidos ao tratamento com anakinra 100 mg/kg i.p. ou infliximabe 5 mg/kgi.p. ou salina i.p., foram tratados 1h após com IFO 400 mg/kg i.p., e 12 h após a IFO foi realizado o sacrifício, com excisão das bexigas para avaliaçãomacroscópica, histopatológica, permeabilidade vascular, mieloperoxidase, contratilidade, cistometrografia e citometria de fluxo para neutrófilos e macrófagos. Alguns animais, antes do sacrifício, foram submetidos a avaliação de nocicepção visceral. Anakinra foi capaz de atenuar hemorragia, edema, infiltrado neutrofílico, hipernocicepção visceral e disfunção vesical...

Hemorrhagic cystitis (HC) induced by ifosfamide (IFO) is an importantclinical complication in patients with cancer. Despite prophylaxis, HC isobserved. The role of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in the pathogenesis of HC provides targets for treatment. Thus, this study aimed to evaluate the protective effect of the IL-1 receptor antagonist (anakinra) and anti-TNF-alpha antibody (infliximab) in experimental HC-induced by IFO in mice. Swiss , C57BL6 , IL -1R-/-, CASP1-/-, TNFR1-/-, TNFR1/R2-/-mice were used. Animals were submitted to pre-treatment with anakinra 100 mg/ kg, ip or infliximab 5 mg/ Kg, ip, or saline ip, 1h after, they were treated with IFO 400 mg/ kg ip, and 12 h after IFO injection they were killed. Then, it was performed resection of the bladder for macroscopic and histopathological evaluation, vascular permeability assay, myeloperoxidase assay, muscle contractility, cistometrogram and flow cytometry to neutrophils andmacrophages. Some animals prior to death, were subjected to evaluation of visceral nociception. Anakinra was able to attenuate hemorrhage, edema, neutrophil infiltration, visceral hypernociception and bladder dysfunction...

Improvement of Erdheim-Chester disease-related renal failure after treatment with anakinra

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by infiltrates of lipid-laden CD68+/CD1- histiocytes, affecting heart, lungs, central nervous system, and bones. Kidney and adjacent structures can also be affected, leading to renal failure in about 30% of cases. The diagnosis is challenging, and treatment is generally based on administration of interferon-alpha (IFNalpha), but preliminary results also showed the therapeutic efficacy of anakinra, an antagonist of the receptor of interleukin-1 (IL-1). We report the case of an elderly patient with ECD and severe involvement of the heart and kidneys who was successfully treated with anakinra.

A Case of Adult Onset Still's Disease with Severe Pneumonitis Treated with Anakinra / 대한내과학회지

Adult onset Still's disease (AOSD) is a systemic autoinflammatory disorder that presents with recurrent fever, extreme fatigue, and joint pain. Pulmonary involvement is not uncommon and, although rare, severe pneumonitis can progress to respiratory failure. Still's disease-associated pneumonitis is generally treated with immunosuppressive agents, but improvement in our understanding of systemic inflammatory processes led us to explore alternative agents. Anakinra is an interleukin-1 receptor antagonist used to treat autoinflammatory disorders resistant to immunosuppressive therapy. Several case reports have demonstrated efficacy of anakinra in treating AOSD, but its relevance in cases complicated with severe pneumonitis has not been examined. Our patient's disease activity was not controlled with systemic steroids and cyclophosphamide. Treatment with anakinra led to a dramatic clinical response. This is the first reported case of AOSD with severe pneumonitis refractory to conventional therapy successfully treated with anakinra.

Two Cases of Refractory Adult-Onset Still's Disease Responding to Anakinra / 대한내과학회지

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with variable clinical features. The interleukin (IL)-1 receptor antagonist anakinra has been proposed as an alternative effective treatment in refractory AOSD. We report, for the first time in Korea, two cases of refractory AOSD in which anakinra treatment produced a clinical response. The first patient had frequent clinical flare-ups with fever, sore throat, myalgia, and pleuritic chest pain despite treatment with methotrexate and etanercept. In the second patient, treatments with various immunosuppressive agents failed to control the disease activity. Treatment with anakinra 100 mg/day was initiated in both cases. A complete clinical remission and improvement in the laboratory parameters were observed. The steroid dose was tapered without further clinical flare-ups. Anakinra appears to be an effective alternative treatment modality in patients with AOSD refractory to conventional disease-modifying anti-rheumatic drugs and corticosteroid therapy.

Two Cases of Refractory Adult-Onset Still's Disease Responding to Anakinra / 대한내과학회지

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with variable clinical features. The interleukin (IL)-1 receptor antagonist anakinra has been proposed as an alternative effective treatment in refractory AOSD. We report, for the first time in Korea, two cases of refractory AOSD in which anakinra treatment produced a clinical response. The first patient had frequent clinical flare-ups with fever, sore throat, myalgia, and pleuritic chest pain despite treatment with methotrexate and etanercept. In the second patient, treatments with various immunosuppressive agents failed to control the disease activity. Treatment with anakinra 100 mg/day was initiated in both cases. A complete clinical remission and improvement in the laboratory parameters were observed. The steroid dose was tapered without further clinical flare-ups. Anakinra appears to be an effective alternative treatment modality in patients with AOSD refractory to conventional disease-modifying anti-rheumatic drugs and corticosteroid therapy.