A bond between rheumatic diseases and cancer in the elderly: The interleukin-6 pathway.

Interleukin (IL)-6 is a soluble factor secreted by T lymphocytes, involved in antibody generation by B lymphocytes. The IL-6 pathway has risen as a pivotal pathway implicated in immune regulation and dysregulation in various rheumatic diseases. Nonetheless, elevated IL-6 levels can also play a role in cancer. Targeting the IL-6 pathway has led to innovative therapeutic approaches for rheumatic diseases and for COVID-19, particularly in the elderly. Indeed, tocilizumab, an agent targeting IL-6, has recently amassed significant attention as a promising univocal agent for different conditions. In this viewpoint, we sought to recall and describe the common pathway among osteoarthritis, rheumatoid arthritis, and cancer, suggesting that anti-IL-6 may be considered a jack-of-all-trades against inflammaging in the elderly.

Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge.

Inflammasomes are multiprotein complexes capable of sensing pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and cellular perturbations. Upon stimulation, the inflammasomes activate the production of the pro-inflammatory cytokines IL-1ß and IL-18 and induce gasdermin D-mediated pyroptosis. Dysregulated inflammasome signaling could lead to hyperinflammation in response to environmental triggers, thus contributing to the pathogenesis of childhood autoimmune/autoinflammatory diseases. In this review, we group childhood rheumatic diseases into the autoinflammation to autoimmunity spectrum and discuss about the involvement of inflammasomes in disease mechanisms. Genetic mutations in inflammasome components cause monogenic autoinflammatory diseases, while inflammasome-related genetic variants have been implicated in polygenic childhood rheumatic diseases. We highlight the reported associations of inflammasome signaling-related genetic polymorphisms/protein levels with pediatric autoimmune disease susceptibility and disease course. Furthermore, we discuss about the use of IL-1 receptor antagonist as an adjunctive therapy in several childhood autoimmune diseases, including macrophage activation syndrome (MAS) and multisystem inflammatory syndrome in children (MIS-C) related to COVID-19. A comprehensive multi-cohort comparison on inflammasome gene expression profile in different pediatric rheumatic diseases is needed to identify patient subsets that might benefit from the adjunctive therapy of IL-1ß inhibitors.