The spectrum and types of adverse side effects to biological immune modulators: a proposal for new classification.

In recent years, a growing number of biological agents such as cytokines, monoclonal antibodies and fusion proteins have become available for the treatment of various autoimmune, neoplastic, cardiovascular, infectious, allergic, and other conditions. Their introduction has resulted in marked clinical improvements for many patients. Nevertheless, a variety of adverse side effects have been observed with these agents. Based on the special features of biological agents a new classification of these side effects of biological agents is proposed--related but clearly distinct from the classification of side effects observed with chemicals and drugs. This classification differentiates five distinct types, namely clinical reactions due to high cytokine levels (type alpha), hypersensitivity due to an immune reaction against the biological agents (type beta), immune or cytokine imbalance syndromes (type gamma), symptoms due to cross-reactivity (type delta), and symptoms not directly affecting the immune system (type epsilon). This classification could help to better deal with the clinical features of these side effects, to identify possible individual and general risk factors and to direct research in this novel area of medicine.