Article
Immunology
Jean-Francois Rossi, Hao-Chun Chiang, Zhao-Yang Lu, Kalle Levon, Frits van Rhee, Karan Kanhai, David C. Fajgenbaum, Bernard Klein
Summary: Standard doses of anti-IL-6 therapy were found to inadequately inhibit IL-6 signaling in patients with COVID-19 or iMCD, resulting in partial inhibition of CRP production. In situations of high IL-6 production, repeated administration of anti-IL-6 therapy was shown to effectively inhibit IL-6 activity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Christine Xu, Ashique Rafique, Terra Potocky, Anne Paccaly, Patrick Nolain, Qiang Lu, Melitza Iglesias-Rodriguez, Gregory St John, Michael C. Nivens, Vanaja Kanamaluru, Jeanette Fairhurst, Tomonori Ishii, Rafael Maldonado, Ernest Choy, Paul Emery
Summary: The study evaluated the inhibition of IL-6 receptor-alpha subunit (IL-6R alpha) signaling by sarilumab and tocilizumab, as well as the association with C-reactive protein (CRP) levels. Sarilumab showed a higher affinity for IL-6R alpha compared to tocilizumab, resulting in higher receptor occupancy (RO) and improved clinical outcomes such as CRP reduction. Higher RO was associated with better disease activity and response in patients receiving sarilumab.
JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Anne J. Paccaly, Pavel Kovalenko, Janie Parrino, Anita Boyapati, Christine Xu, Hubert van Hoogstraten, Tomonori Ishii, John D. Davis, A. Thomas DiCioccio
Summary: In this study, pharmacokinetics, pharmacodynamics, and PK/PD relationships of two different drugs for rheumatoid arthritis patients were evaluated. The onset of efficacy and safety profiles were similar for both drugs, despite differences in pharmacokinetics. This suggests that subcutaneous sarilumab and intravenous tocilizumab have comparable effects in reducing inflammation and maintaining white blood cell count in patients with inadequate responses to methotrexate.
JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Medicine, General & Internal
Eun-Hwa Lee, Kyoung-Hwa Lee, Young-Goo Song, Sang-Hoon Han
Summary: C-reactive protein (CRP) or procalcitonin (PCT) alone have limitations in the early detection of infection or inflammation. Interleukin (IL)-6 has been assessed recently, and this study reveals considerable discrepancies among CRP, PCT, and IL-6 levels. Relying solely on CRP tests may lead to misinterpretation.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
Blanka Wolszczak-Biedrzycka, Justyna Dorf, Anna Milewska, Mateusz Lukaszyk, Wojciech Naumnik, Jakub Wiktor Kosidlo, Violetta Dymicka-Piekarska
Summary: This study evaluated the diagnostic value of inflammatory markers for assessing COVID-19 patients with different severity of symptoms. The concentrations of CRP and IL6 were determined, and ratios of CRP/IL6, CRP/L, and LCR were calculated. The results showed that these inflammatory markers significantly increased with disease progression based on the MEWS and could be used to differentiate between severe and non-severe COVID-19 patients and assess mortality.
JOURNAL OF INFLAMMATION RESEARCH
(2023)
Article
Medicine, General & Internal
Laura Castelnovo, Antonio Tamburello, Alfredo Lurati, Eleonora Zaccara, Maria Grazia Marrazza, Micol Olivetti, Nicola Mumoli, Daniela Mastroiacovo, Daniele Colombo, Elisabetta Ricchiuti, Paolo Vigano', Faggioli Paola, Antonino Mazzone
Summary: Tocilizumab and sarilumab may be effective in treating COVID-19 pneumonia, reducing mortality rates. Anti-IL6 drugs can decrease inflammation levels, shorten hospitalization times, and reduce the risk of death from multi-organ failure. However, further research is needed to determine the optimal treatment timing.
Review
Cardiac & Cardiovascular Systems
Paul M. Ridker, Manas Rane
Summary: IL-6 is a pivotal cytokine in innate immunity with a proatherogenic role in cardiovascular disease. Research has explored mechanisms of IL-6 signaling, murine models, and human epidemiological data regarding its utility as a biomarker of vascular risk.
CIRCULATION RESEARCH
(2021)
Review
Medicine, Research & Experimental
Lucinda Villaescusa, Francisco Zaragoza, Irene Gayo-Abeleira, Cristina Zaragoza
Summary: This article provides data to support the use of drugs targeting IL-6 as a rational approach to treat severe respiratory complications in COVID-19 patients. Specifically, the monoclonal antibody siltuximab has been shown to reduce IL-6 levels and attenuate the inflammatory response in these patients.
ADVANCES IN THERAPY
(2022)
Article
Oncology
Jiuhui Xu, Chenglong Chen, Kunkun Sun, Qianyu Shi, Boyang Wang, Yi Huang, Tingting Ren, Xiaodong Tang
Summary: This study found that interleukin-6 (IL-6) and its downstream pathway STAT3 were activated in anlotinib-resistant osteosarcoma. Tocilizumab, an anti-IL-6 receptor drug, can block tumor progression in anlotinib-resistant OS cells by inhibiting STAT3 expression. Combination treatment with anlotinib enhances these effects. IL-6 is highly expressed in osteosarcoma patients and is associated with poor prognosis.
FRONTIERS IN ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Annett Klinder, Janine Waletzko-Hellwig, Marie-Luise Sellin, Anika Seyfarth-Sehlke, Markus Wolfien, Franziska Prehn, Rainer Bader, Anika Jonitz-Heincke
Summary: This study investigated the effects of IL-6 receptor blockade on the differentiation of human primary osteoblasts. The results showed that sarilumab can inhibit IL-6/sIL-6R-induced osteogenic differentiation and gene expression related to bone matrix maintenance.
Article
Cardiac & Cardiovascular Systems
Anu Kataja, Tuukka Tarvasmaki, Johan Lassus, Alessandro Sionis, Alexandre Mebazaa, Kari Pulkki, Marek Banaszewski, Valentina Carubelli, Mari Hongisto, Ewa Jankowska, Raija Jurkko, Toni Jantti, Monika Kasztura, John Parissis, Tuija Sabell, Jose Silva-Cardoso, Jindrich Spinar, Heli Tolppanen, Veli-Pekka Harjola
Summary: Inflammatory markers, particularly PCT and IL-6, are strongly associated with signs of systemic hypoperfusion in cardiogenic shock (CS) and predict poor prognosis. High levels of PCT and IL-6 are linked to increased 90-day mortality rates, while CRP levels do not show significant prognostic value.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2021)
Article
Medicine, General & Internal
Robert Flisiak, Jerzy Jaroszewicz, Magdalena Rogalska, Tadeusz Lapinski, Aleksandra Berkan-Kawinska, Beata Bolewska, Magdalena Tudrujek-Zdunek, Dorota Kozielewicz, Marta Rorat, Piotr Leszczynski, Krzysztof Klos, Justyna Kowalska, Pawel Pabjan, Anna Piekarska, Iwona Mozer-Lisewska, Krzysztof Tomasiewicz, Malgorzata Pawlowska, Krzysztof Simon, Joanna Polanska, Dorota Zarebska-Michaluk
Summary: The study demonstrated the significant impact of tocilizumab on reducing mortality and accelerating clinical improvement in COVID-19 patients with a baseline concentration of IL-6 > 100 pg/mL, particularly those who require oxygen supplementation.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Endocrinology & Metabolism
Maria Krajewska, Ewelina Witkowska-Sedek, Malgorzata Ruminska, Anna Stelmaszczyk-Emmel, Maria Sobol, Anna Majcher, Beata Pyrzak
Summary: The study found that vitamin D supplementation had beneficial effects in overweight and obese children, reducing inflammation levels and stabilizing anti-inflammatory cytokines.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Immunology
Joshua H. Cho, Saumya Bhutani, Carole H. Kim, Michael R. Irwin
Summary: This review examined the potential of exogenous melatonin in reducing inflammatory markers in humans. Results showed significant anti-inflammatory effects of melatonin on certain markers, suggesting its potential as a preventative and adjunct treatment for inflammatory disorders in older populations.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Immunology
Marijne Vandebergh, Sara Becelaere, Benedicte Dubois, An Goris, CHARGE Inflammation Working Grp
Summary: This study identified IL-6 signaling as a major mediator of the association between BMI and risk of MS. The proportion of the effect of BMI on MS mediated by IL-6 signaling corresponded to 43%. In contrast to IL-6 signaling, there was little evidence for an effect of serum IL-6 levels or CRP levels on the risk of MS.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Evangelos Andreakos, Laurent Abel, Donald C. Vinh, Elzbieta Kaja, Beth A. Drolet, Qian Zhang, Cliona O'Farrelly, Giuseppe Novelli, Carlos Rodriguez-Gallego, Filomeen Haerynck, Carolina Prando, Aurora Pujol, Helen C. Su, Jean-Laurent Casanova, Andras N. Spaan, Paul Bastard, Catherine M. Biggs, Benedetta Bigio, Bertrand Boisson, Alexandre Bolze, Anastasiia Bondarenko, Petter Brodin, Samya Chakravorty, John Christodoulou, Aurelie Cobat, Antonio Condino-Neto, Stefan N. Constantinescu, Hagit Baris Feldman, Jacques Fellay, Rabih Halwani, Emmanuelle Jouanguy, Yu-Lung Lau, Isabelle Meyts, Trine H. Mogensen, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarstrom, Anna M. Planas, Anne Puel, Lluis Quintana-Murci, Laurent Renia, Igor Resnick, Anna Sediva, Anna Shcherbina, Ondrej Slaby, Ivan Tancevski, Stuart E. Turvey, K. M. Furkan Uddin, Diederik van de Beek, Mayana Zatz, Pawel Zawadzki, Shen-Ying Zhang
Summary: SARS-CoV-2 infections can vary greatly between individuals, with some being asymptomatic while others experience life-threatening disease. While 20% of critical COVID-19 cases are due to inborn errors or autoantibodies, the genetic and immunological factors for resistance to infection itself remain unknown. Studies have shown that autosomal recessive deficiencies in certain genes or enzymes can confer resistance to diseases, suggesting a potential strategy for identifying individuals naturally resistant to SARS-CoV-2 infection.
Review
Immunology
Angela Deya-Martinez, Jaques G. Riviere, Persio Roxo-Junior, Jan Ramakers, Marketa Bloomfield, Paloma Guisado Hernandez, Pilar Blanco Lobo, Soraya Regina Abu Jamra, Ana Esteve-Sole, Veronika Kanderova, Ana Garcia-Garcia, Mireia Lopez-Corbeto, Natalia Martinez Pomar, Andrea Martin-Nalda, Laia Alsina, Olaf Neth, Peter Olbrich
Summary: This study retrospectively examined pediatric patients with STAT1 GOF who received JAKinib treatment and found potential benefits of JAKinibs for this population. However, further research is needed to establish indications, dosing, and monitoring of JAKinibs.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Hematology
V. Koneti Rao, Sharon Webster, Anna Sediva, Alessandro Plebani, Catharina Schuetz, Anna Shcherbina, Niall Conlon, Tanya Coulter, Virgil A. Dalm, Antonino Trizzino, Yulia Zharankova, Elaine Kulm, Julia Koerholz, Vassilios Lougaris, Yulia Rodina, Kath Radford, Jason Bradt, Klaus Kucher, Anurag Relan, Steven M. Holland, Michael J. Lenardo, Gulbu Uzel
Summary: Activated phosphoinositide 3-kinase delta (PI3K delta) syndrome (APDS) is a genetic disorder that results in immune dysregulation and deficiency. In a clinical trial, leniolisib, a selective PI3K delta inhibitor, was found to improve lymphadenopathy and increase the percentage of naive B cells in patients with APDS, demonstrating a positive impact on their immune system. Overall, leniolisib was well tolerated with minimal adverse events.
Article
Immunology
Zuzana Parackova, Irena Zentsova, Petra Vrabcova, Anna Sediva, Marketa Bloomfield
Summary: STAT1 GOF mutations are responsible for chronic mucocutaneous candidiasis (CMC) and autoimmune manifestations. Our study shows that these mutations affect the properties of dendritic cells (DCs) and alter their functions. The altered DCs lose their tolerogenic functions, become proinflammatory, and have decreased ability to induce Th17 cells. The results suggest that DCs play a direct role in the immune pathology associated with STAT1 GOF mutations.
CLINICAL IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Jiri Bronsky, Ivana Copova, Marianna Durilova, Denis Kazeka, Michal Kubat, Tereza Lerchova, Eva Vlckova, Katarina Mitrova, Michal Rataj, Adam Klocperk, Anna Sediva, Ondrej Hradsky
Summary: This study aimed to compare the postvaccination immunity of mRNA BNT162b2 SARS-CoV-2 vaccine in pediatric patients with inflammatory bowel disease (IBD) over 12 years old to healthy controls and identify predictors of its robustness. The results showed that patients with IBD had higher levels of anti-receptor binding domain and anti-S2 antibodies compared to controls, and these levels were associated with time since vaccination, history of SARS-CoV-2 infection, and anti-tumor necrosis factor treatment.
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2023)
Article
Allergy
Tomas Milota, Jitka Smetanova, Aneta Skotnicova, Michal Rataj, Jan Lastovicka, Hana Zelena, Zuzana Parackova, Martina Fejtkova, Veronika Kanderova, Eva Fronkova, Katerina Rejlova, Anna Sediva, Tomas Kalina
Summary: Patients with CVID showed measurable antibody and T-cell immune responses after receiving the BNT162b2 vaccine, but the antibody titers were low and decreased rapidly, while the T-cell response remained stable. The vaccine demonstrated favorable safety and clinical outcomes in preventing severe COVID-19.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Review
Pediatrics
Iva Pospisilova, Helena L. Brodska, Marketa Bloomfield, Klara Borecka, Jan Janota
Summary: This study evaluated the efficacy of presepsin (P-SEP) as a potential biomarker for early-onset neonatal sepsis (EOS) and compared it to other commonly used markers of inflammation. The study found that plasma P-SEP levels were significantly higher in newborns with probable infection compared to healthy newborns and those with unlikely infection. When combined with IL-6 and CRP, P-SEP showed the highest diagnostic efficacy for EOS. The optimal cut-off value for P-SEP was determined to be 695 ng/L.
FRONTIERS IN PEDIATRICS
(2023)
Article
Multidisciplinary Sciences
Adriana A. de Jesus, Guibin Chen, Dan Yang, Tomas Brdicka, Natasha M. Ruth, David Bennin, Dita Cebecauerova, Hana Malcova, Helen Freeman, Neil Martin, Karel Svojgr, Murray H. Passo, Farzana Bhuyan, Sara Alehashemi, Andre T. Rastegar, Katsiaryna Uss, Lela Kardava, Bernadette Marrero, Iris Duric, Ebun Omoyinmi, Petra Peldova, Chyi-Chia Richard Lee, David E. Kleiner, Colleen M. Hadigan, Stephen M. Hewitt, Stefania Pittaluga, Carmelo Carmona-Rivera, Katherine R. Calvo, Nirali Shah, Miroslava Balascakova, Danielle L. Fink, Radana Kotalova, Zuzana Parackova, Lucie Peterkova, Daniela Kuzilkova, Vit Campr, Lucie Sramkova, Angelique Biancotto, Stephen R. Brooks, Cameron Manes, Eric Meffre, Rebecca L. Harper, Hyesun Kuehn, Mariana J. Kaplan, Paul Brogan, Sergio D. Rosenzweig, Melinda Merchant, Zuoming Deng, Anna Huttenlocher, Susan L. Moir, Douglas B. Kuhns, Manfred Boehm, Karolina Skvarova Kramarzova, Raphaela Goldbach-Mansky
Summary: Neutrophilic inflammation is a common feature in many genetic autoinflammatory diseases. This study presents three cases of newborns with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation, and identified novel variants in the Src-family tyrosine kinase LYN that lead to Lyn kinase activation. The research highlights the critical role of Lyn kinase in modulating inflammatory signals, regulating microvascular permeability, neutrophil recruitment, and promoting hepatic fibrosis.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Zuzana Parackova, Petra Vrabcova, Irena Zentsova, Anna Sediva, Marketa Bloomfield
Summary: STAT1 gain-of-function (GOF) mutations lead to an inborn error of immunity with a wide range of manifestations, including chronic mucocutaneous candidiasis (CMC) and non-infectious complications such as autoimmunity and vascular issues. This study focuses on the role of neutrophils in the immunodysregulation and vascular pathology associated with STAT1 GOF CMC. The results suggest that STAT1 GOF neutrophils exhibit immature and highly activated phenotypes, with increased propensity for degranulation, NETosis, and platelet-neutrophil aggregation.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Correction
Rheumatology
J. Smetanova, Z. Strizova, A. Sediva
LANCET RHEUMATOLOGY
(2023)