Perspectives in immunopharmacology: The future of immunosuppression

• Although the expansion of new strategies and molecules for achieving immunosuppression has improved the quality of life of many patients suffering from tumors, immune-related and degenerative diseases, curing these illnesses is a goal still far from being reached
• The future trends of immunopharmacology aim at curative interventions, with the help of the information techniques and technologically advanced tools, by three major approaches.
• Human immunology. Immunological mechanisms underlying diseases must be studied in humans and/or with representative in vitro models based on primary human cells or tissue-like cultures, or with accurately predictive in vivo models. Personalized intervention is a particularly important strategy in immunomodulation.
• Re-education of detrimental immune responses. Rather than immunosuppressive or cytocidal treatments that eliminate detrimental immunity, the new goal of immunopharmacology is that of re-educating anomalous immunity towards normal defensive reactivity, thereby achieving a real cure.
• Tolerisation. A key issue in immune re-education is the induction of tolerance vs. self- or innocuous antigens that are triggering autoimmune and allergic pathologies. Re-establishing tolerance towards such antigens will eliminate the cause of the disease and achieve the complete cure.

Modulation of immune responses for therapeutic purposes is a particularly relevant area, given the central role of anomalous immunity in a wide variety of diseases, from the most typically immune-related syndromes (autoimmune diseases, allergy and asthma, immunodeficiencies) to those in which altered immunity and inflammation define the pathological outcomes (chronic infections, tumors, chronic inflammatory and degenerative diseases, metabolic disorders, etc.).This brief review will summarize some of the most promising perspectives of immunopharmacology, in particular in the area of immunosuppression, by considering the following aspects:–molecular pathways: investigating the fine mechanisms of immune modulation, to define novel targets and new clinical applications, with particular emphasis to approaches for re-education of anomalous immunity, including induction of tolerance.–personalized medicine: how pharmacogenomics can help in selecting the optimal treatment for each patient, focusing on human immunology for obtaining relevant information that animal models cannot provide.–microbiome: considering immune responses as the result of the interaction between human cells and commensal bacteria, for a new perspective in the use of immunosuppressive treatments.–natural products: providing a scientific basis to the huge body of pharmacological knowledge and products of traditional medicine for identifying new active molecules and new treatment concepts.–nanomedicine: exploiting the intelligent design of engineered nanoparticles offered by nanotechnologies in tailoring shape-, size-, surface-controlled carriers for targeted delivery of drugs.