anakinra (PerkinRA)

Controlled Release of the IL-1R Antagonist, Anakinra, from Microgels with an Extended Intra-articular Residence Time.

Trujillo Ruben J RJ, Lok Sara S, Bonassar Lawrence J LJ, Putnam David D

To establish intra-articularly injected microgel compositions that can control the rate of release of anakinra, a protein-based IL-1R antagonist, at therapeutically relevant concentrations for an extended period of time. Uptake and release of the IL-1Ra from microgels was tuned by simple post-synthesis modifications via the addition of calcium chloride after protein loading, or conjugation of small molecules to existing microgels to study the effects of negative (unmodified), positive (dimethylethylenediamine, agmatine), polar (ethanolamine), and non-polar (phenethylamine) side chains on protein delivery. Microgels modified with phenethylamine enhanced the loading capacity of the IL-1Ra to 242%. Both calcium-treated and small molecule-modified microgels had a decrease in initial burst release from the microgel matrix, and both extended the release of IL-1Ra from 6 h for unmodified microgels to over 60 days within the active therapeutic index of the drug. Microgels persist in the joint space for at least 8 weeks, and follow a bi-exponential decay curve with a ß half-life of 93.2 days. These findings demonstrate the application of simple post-synthesis modifications for improved drug delivery via polyanionic microgels, and support the potential use of poly(acrylic acid) microgels as intra-articular drug delivery vehicles for osteoarthritis treatment.

Oxycodone self-administration in rats differentially alters IL-1R1 and IL-1R2 expression in the brain.

Dunn Scott D SD, Abiru Memunat M, Stern Danielle D, McCafferty Mary M et al.

Interleukin 1β (IL-1β) is a proinflammatory cytokine that binds to two receptors, IL-1R1 and IL-1R2. IL-1R1 activation initiates neuroinflammation, and IL-1R2 is a decoy receptor that reduces IL-1R1 signaling by sequestering IL-1β. Emerging evidence links IL-1β to substance use disorders. Methamphetamine and ethanol increase IL-1β levels in the brain, and antagonism of IL-1β signaling reduces negative affective behaviors caused by methamphetamine and ethanol. However, effects of chronic opioid exposure on the IL-1β system in the brain and blocking IL-1β signaling on rewarding effects of opioids are unknown. We determined if oxycodone self-administration (SA) causes brain-region specific changes in IL-1β, IL-1R1, and IL-1R2 levels (mRNA and protein) and if antagonizing IL-1β signaling affects oxycodone SA behaviors. Following 14 days of oxycodone SA (0.056 mg/kg/inf), IL-1R2 mRNA levels were increased in the basolateral amygdala (BLA) and IL-1R1 mRNA levels in the BLA were decreased. For IL-1β itself, oxycodone SA did not affect mRNA levels. Oxycodone SA also did not alter protein levels of IL-1R2, IL-1R1, pro-IL-1β, mature-IL-1β, or the relative expression ratios between pro- and mature-IL-1β. Systemic administration of anakinra, an IL-1R1 antagonist, did not block acquisition of oxycodone SA. Intracerebroventricular (ICV) administration of anakinra following oxycodone acquisition did not reduce oxycodone SA and infusions. Our results show that oxycodone SA induces notable changes in IL-1 receptor mRNA in the BLA but is not affected by pharmacological antagonism of IL-1β signaling.

Recurrent non-infectious inflammatory endocarditis effectively treated with anakinra: a case report.

Chiara Emanuele E, Canfora Maria M, Stefano Pierluigi P, Del Pace Stefano S et al.

Precision immunomodulation for pediatric hemophagocytic lymphohistiocytosis in intensive care.

Lilitwat Weerapong W, Bhandari Prakreeti P

Hemophagocytic lymphohistiocytosis (HLH) and related cytokine storm syndromes are life-threatening hyperinflammatory disorders that frequently intersect with pediatric critical care. Critically ill children may present with fever, shock, cytopenias, liver dysfunction, coagulopathy, hyperferritinemia, respiratory failure, neurologic deterioration, and multiple organ dysfunction, creating substantial overlap with severe sepsis. Traditional diagnostic criteria remain foundational but do not identify the dominant mechanism or optimal therapy for an individual child. In this review, precision immunomodulation is defined operationally as matching the suspected trigger and clinical phenotype with pathway-informed biomarkers when available, drug-delivery feasibility during organ failure, and the plan for definitive disease control. Interferon-gamma activity may be supported by CXCL9; interleukin (IL)-1/IL-18 biology may support anakinra in macrophage activation syndrome; broader cytokine signaling may support Janus kinase inhibition in selected refractory HLH; and IL-6-directed therapy is primarily syndrome- and grade-directed in immune effector cell cytokine release syndrome. These markers are supportive rather than validated treatment thresholds. Targeted therapy must proceed alongside antimicrobial therapy, source control, organ support, infection surveillance, and early hematopoietic stem cell transplantation planning when indicated. This review provides a bedside framework for phenotype assignment, biomarker interpretation, intensive care unit-focused targeted therapy, extracorporeal bridge strategies, and reassessment at 24-72 h.