Biologics

Interleukin-6 (IL-6) is a multifunctional cytokine with an essential role in immunity, inflammation, and cancer. Produced by immune, stromal and epithelial cells in response to infection or tissue stress, IL-6 regulates immune responses, acute-phase proteins (including serum amyloid A and C-reactive protein), hematopoiesis, and tissue remodeling. These effects are mediated via classical and trans-signaling pathways, which activate key intracellular cascades such as JAK/STAT3, MAPK, and PI3K/AKT. Accumulating evidence implicates dysregulated IL-6 signaling in both oncologic and infectious diseases, where it contributes to disease progression, immune evasion, and therapeutic resistance. This review aims to critically examine the role of IL-6 as a biomarker and therapeutic target in these two major clinical contexts: in cancer, IL-6 levels reflect tumor burden, prognosis, and therapy resistance in both adult and pediatric patients; in infectious diseases, circulating IL-6 may support early diagnosis and risk stratification, particularly in vulnerable pediatric populations. By integrating molecular mechanisms with clinical evidence, this review highlights IL-6 as a unifying biomarker linking inflammation, infection, and malignancy. It also addresses current limitations, including assay variability, lack of standardized reference ranges, especially in children, and challenges in clinical implementation.

Background/Objectives: The rates and predictors of clinical remission, a novel and practical therapeutic goal in severe asthma, have been inconsistently reported across studies. Data on clinical remission in Japanese patients remain limited. The aim of this study was to assess the rate of four-component clinical remission and its predictors in Japanese adult patients with severe asthma. Methods: This retrospective study enrolled adult patients with severe asthma who had initiated biologic therapy at least 12 months prior to inclusion at Nagoya City University Hospital. The primary endpoint was the achievement rate of four-component clinical remission, defined as (1) no maintenance oral corticosteroids (OCS); (2) no exacerbations for 12 months; (3) Asthma Control Test (ACT) score ≥ 20; and (4) forced expiratory volume in one second (FEV₁) ≥ 80% of predicted. The secondary endpoint was to identify factors, including airway structural indices measured using chest computed tomography (CT), associated with clinical remission at 12 months. Results: Among 87 patients with severe asthma, 26 (30%) achieved four-component clinical remission after 12 months of biologic therapy. In univariate analysis, clinical remission was more frequently achieved in patients with chronic rhinosinusitis, higher FEV₁ (% predicted), higher blood eosinophil counts, higher ACT scores, fewer exacerbations in the previous year, higher Lund–Mackay scores, and smaller airway wall thickness and luminal areas on CT (all p < 0.05). Multivariate analysis revealed that higher blood eosinophil counts and fewer exacerbations in the previous year were independently associated with clinical remission (both p < 0.05). Conclusions: After 12 months of biologic therapy, 30% of patients with severe asthma achieved four-component clinical remission. Higher blood eosinophil counts and fewer prior exacerbations were associated with higher remission rates.

The complement system is a key component of innate immunity, responsible for mediating the rapid clearance of pathogens and coordinating adaptive immune responses. Although complement activation is essential for effective infection control and prevention, its excessive or dysregulated function contributes to the pathogenesis of various immune-mediated disorders. Therefore, therapeutic inhibition of the overactive complement cascade, in which specific components are selectively blocked to suppress pathological activation, plays an important role in the treatment of various complement (immune)-mediated diseases. This article provides an overview of complement inhibition as a therapeutic strategy, highlighting the infectious risks associated with its use. Disruption of complement-dependent host defence mechanisms increases the risk of invasive infections (caused by encapsulated pathogens, e.g., Neisseria spp., Streptococcus pneumoniae and Haemophilus influenzae type B), which represent a significant clinical challenge. Therefore, the use of complement inhibition should not only be effective but also safe in combination with the application of all possible tools to prevent infections. Strategies, such as vaccination and antibiotic prophylaxis, are crucial to minimise these complications, despite the persistence of the risk of breakthrough infections. Furthermore, this review examines advancements in patient risk stratification, evaluates alternative preventive measures, and identifies key gaps in current clinical practice. Future directions include improving monitoring protocols, creating more selective or locally acting complement inhibitors, and implementing biomarker-driven personalised therapies that maximise benefits while reducing side effects.