Neuroimmunomodulation: effects of stress and central nervous system acting drugs on immune/inflamatory response

Abstract

The field of neuroimmune interactions is a prime example of interdisciplinary research spanning immunology, neurobiology, neuroendocrinology, and behavioral sciences. It also exemplifies research from the molecular to the clinical domain. The greatest challenge of the field, which this project seeks to study and stimulate, is research that is at the same time precise, focused and integrative. Thus, several lines of interdisciplary overlap between nervous and immune systems will be analyzed m the present Thematic Project. Most extensively studies will be linked to immune cells/cytokine-neuropeptide/neurotransmitter interactions. More precisely, it is our intention to analyze and to understand the effects of disruptions of neuroimmune interactions on disease susceptibility; specifically, it is our intention to help the classification of how perturbations of one system, such as stimulation of the neuroendocrine stress response and/or the use of central nervous system (CNS) acting drugs, might affect the expression of diseases and, in the other, how immune/inflammatory or infectious diseases affect behavior. Althought the question of how emotions affect diseases has intrigued both popular culture and academic medicine for milenia, now, more than ever before, we have the technological tools to analyze them more properly. Indeed, we can quantitate, dissect, and define the behavioral and immunological/inflammatory phenomena, trace their molecular and anatomical underpinnings, and prove by accurate interventions what kind of disruptions in the communication between these systems might lead to disease. One could argue that the present proposed analysis are not new, since mankind bas so long been aware of a relationship between emotions and disease, i.e., that we are simply changing the terminology from the "humors" of Galeno and Hippocrates' times to the molecules and nerve pathways of the 1990s. This is true; but it is also true that the new technologies we can now use, a flow us to rediline old questions at increasingly precise magnifications. What is new are the possibilities that such precise knowledge might bring for a better prevention and treatment of diseases. Indeed, it is our understanding that experimental analysis of the multiple level of interaction of the immune and nervous system (including effects of cytokines on behavior and effects of CNS acting drugs and behavioral models, such as stress, anxiety and depression, on immune/inflammatory events) will allow more intelligent design of drugs to treat diseases that occur as a result of a breakdown at the interface of the interaction between these two systems. And, by understanding the many molecular and environmental variables that regulate these interactions, we will be able to achieve a level of fine tuning of these systems to better modulate diseases.Sixteen different and interconnected experimental designs - some of them subject of MS or PhD dissertations now being prepared in our Department -are the objective of the present Thematic Project. They are: I - effects of haloperidol on Ehrlich tumor development: an experimental evaluation of the immune/inflammatory response; 2 - effects of diazepam on Ehrlich tumor development: an experimental analysis of the ascitic tumoral form; 3 - effects of an experimental model of depression on Ehrlich tumor development and on peritoneal macrophage activity; 4 - effects of prenatal stress on Ehrlich tumor development; 5 - effects of diazepam plus amphetamine treatments on experimental tuberculosis evolution in hamsters; 6 - effects of prenatal diazepam treatment on experimental tuberculosis evolution in hamsters; 7 -neuroimmunomodulation: effects of diazepam treatment on immune response of chicks; 8 - effects of prenatal diazepam treatment on physical and behavioral landmarks of development and on peritoneal macrophage activity of rats; 9 - effects of diazepam treatment on macrophage activity of mice; 10 - effects of prenatal stress on macrophage activity and corticosterone serum levels of rats; 11 - effects of diazepam treatment on carragenin-induced acute inflammatory responses in rats; 12 - behavioral evaluation of rats submitted to an anaphilatic conditioning: interactions among anxiety, immunity and diazepam effects; 13 - interactions between CNS and hypersensitivity to egg-albumin in rats; 14 - effects of an inescapable foot shock stress on bronco-alveolar inflammatory response on rats made hipersensitivity to egg-albumin; 15 - effects of carbamazepin on some experimental models of inflammation; 16 - effects of prenatal interleukin-1 (IL-1) administration on striatal dopaminergic activity of rats: behavioral and neurochemical evaluations. (AU)