Innate and Adaptive Immune Mechanisms in Pericarditis: Pathobiology and Clinical Implications

Pericarditis is an inflammatory disorder of the pericardium with a broad clinical spectrum, ranging from a single acute episode to recurrent, incessant, or chronic disease. Although most cases are idiopathic and self-limited, a subset of patients develop relapsing or treatment-resistant pericarditis marked by persistent inflammation, tissue remodelling, and, in severe cases, constrictive physiology. These clinical phenotypes support a model where pericarditis represents a spectrum of immune-mediated disease. In this review, we integrate clinical classification with emerging insights into innate and adaptive immunity to bridge pericarditis immunopathology with clinical presentation. Acute idiopathic pericarditis is commonly initiated by innate danger sensing through pattern-recognition receptors, triggering nuclear factor κB activation, NLRP3 inflammasome assembly, and interleukin (IL) 1α/1β driven inflammation. In recurrent disease, sustained activation of these pathways can establish self-amplifying inflammatory circuits involving IL-1, IL-6, tumor necrosis factor α, and JAK/STAT signalling, promoting leukocyte recruitment and fibroblast activation. Emerging clinical and serologic evidence further suggests that adaptive immune mechanisms contribute to disease persistence. These observations highlight that recurrent pericarditis exists along a continuum from predominantly autoinflammatory to mixed autoinflammatory and autoimmune disease. Insights from preclinical models, including viral, sterile inflammasome driven, cytokine-mediated, and autoimmune models, have validated these pathways and clarified mechanisms of pericarditis and its complications. This mechanistic understanding has strengthened the biological rationale underlying current therapeutic approaches. IL-1 inhibition has emerged as a paradigm-shifting treatment for recurrent pericarditis, whereas IL-6 blockade, JAK inhibition, and broader immunosuppression may benefit selected phenotypes. Future research should focus on defining immune endotypes, identifying predictive biomarkers, and aligning targeted therapies with the dominant inflammatory drivers.