Immunopharmacology: a new frontier

Immunopharmacology is a hybrid science which has been founded upon the principles, theory, and technical developments of both immunology and pharmacology, but which has a unique identity incorporating both basic and applied areas of research. Basic immunopharmacological research is concerned with the underlying mechanisms by which endogenous and synthetic chemicals interact with the cells of the immune system. Important areas of research include the actions of chemicals such as lymphokines, cytokines, complement, kinins, autacoids, drugs, and even neuropeptides on immune function. Applied immunopharmacology is concerned with the development and testing of new immunomodulatory drugs which will be of benefit to clinical medicine but also as basic research tools. In the past, the two fields of immunology and pharmacology have contributed to each other in many significant ways. Immunology has contributed to pharmacological research by the development of antibodies which are frequently used today as specific probes for the quantitative and qualitative analysis of many different classes of chemicals of interest. Pharmacology has contributed to the field of immunology by providing basic pharmacological information on subjects such as the mediators of hypersensitivity reactions and inflammation. In the future, the truly hybrid field of immunopharmacology promises to have an expanding role in clinical medicine and basic research. This prediction is based on the observation that recombinant lymphokines and newly discovered immunomodulatory substances have begun to enter the clinic in ever increasing numbers. Future immunopharmacological research will include the study of the pharmacology of these lymphokines but also the rational development of new drugs that act as antagonists or agonists for the endogenous lymphokines that normally regulate the immune response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tyrosinosis: a new variant

Abnormalities of tyrosine metabolism are discussed under four headings: (1) accumulation of tyrosine and its metabolites secondary to severe liver damage, vitamin C deficiency, etc.; (2) transient neonatal tyrosinemia; (3) hereditary tyrosinosis with hepatorenal dysfunction where elevation of tyrosine and methionine levels in the plasma may be a secondary manifestation of an unknown disease process; and (4) “essential tyrosinemia” or tyrosinosis without hepatorenal dysfunction which may represent a kkrimary fault in the metabolism of tyrosine.A new case of tyrosinosis without hepatorenal dysfunction in a 13-year-old mentally retarded girl is reported. Clinical findings, laboratory investigations and results of dietary management and normalization of the plasma tyrosine level and of urinary metabolites are presented and compared with the features of three similar cases in the liteature. It is suggested that these cases represent “essential tyrosinemia” where there is a primary genetic defect in tyrosine metabolism.     

ER-mediated phagocytosis: a new membrane for new functions

Genomics and other high-throughput approaches, such as proteomics, are changing the way we study complex biological systems. In the past few years, these approaches have contributed markedly to improving our understanding of phagocytosis. Indeed, the ability to study biological systems by monitoring hundreds of proteins provides a level of resolution that is not attainable by the usual 'one protein at a time' approach. In this article, I discuss how proteomic approaches have revealed surprising findings that enable us to revisit established concepts, such as the origin of the phagosome membrane, and to propose new models of cell organization and the link between innate and adaptive immunity.     

Photopheresis: a new therapeutic concept

Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (8-MOP), is a new treatment for disorders caused by aberrant T lymphocytes. It is now a standard therapy for advanced cutaneous T-cell lymphoma and shows promise in the treatment of two autoimmune disorders, pemphigus vulgaris and progressive systemic sclerosis (scleroderma). Additional diseases for which clinical trials are in progress include multiple sclerosis, organ transplant rejection, rheumatoid arthritis, and AIDS. The mechanism of action appears to involve a "vaccination" against the pathogenic T cells, in a clone-specific manner. Photoactivated 8-MOP initiates a cascade of immunologic events by forming covalent photoadducts with nuclear and cell surface-adherent DNA and possibly with other cellular molecules. For reasons not yet fully clarified, but probably related to enhanced cycling of the T-cell receptor for antigen, photopheresis increases the immunogenicity of the irradiated T cells so that their reinfusion induces a therapeutically significant immunologic reaction that targets unirradiated T cells of the pathogenic clone(s). The specificity of the induced immunologic reaction probably results from the extremely disproportionate expansion of the pathogenic clone(s), relative to the several million other clones of normal T cells.