International Trends in Immunity

The core of biological agents recently introduced in human therapy includes Monoclonal Antibodies, Fusion proteins and a number of Cytokines employed in monotherapy or in association with conventional drugs. Their extraordinary impact in oncologic, autoimmune, and inflammatory diseases is impressive. However, they are usually accompanied by a complex profile of Drug-Related Adverse Events (DRAEs) with peculiar characteristics, mostly related to the proteic nature of these new agents often targeting crucial components and receptors of the immune system. Such interaction ultimately induces local and systemic reactions generated by activating or inhibiting signals, leading to cell hyperactivation and destruction, immunosuppression, eventually followed by immune rebounds after therapy discontinuation. Among the clinical consequences of DRAEs, a number of systemic syndromes are of particular concern for their rapid insurgence and severity, although expressed in a limited number of patients. We consider here eight different clinical expressions, namely the Capillary Leak Syndrome (CLS), the Cytokine Release Syndrome (CRS), the Infusion Reaction Syndrome (IRS), the Tumor Lysis Syndrome (TLS), the Systemic Inflammatory Response Syndrome, (SIRS), the Macrophage Activation Syndrome (MAS), the Immune Reconstitution Inflammatory Syndrome (IRIS), and the Immune-related Adverse Events Syndrome (IrAES) not only for their clinical relevance, but also as paradigmatic examples of the mechanisms of action (MOAs) involved during biomedicine’s therapeutic administrations. From the analysis and confrontation of both clinical features and the twine of interacting MOAs in each syndrome, it emerges a common pathogenetic background consisting in a dynamic imbalance of the cytokines network, where pro-inflammatory molecules prevail, thus generating different systemic expressions based on a common pivotal event here defined as Cytokine Dysregulation Status/Syndrome (CDS). Such pathogenetic interpretation if offered with the aim of stimulating further investigation and debate.