The objective of this research proposal is to evaluate the role of central nervous system (CNS) catecholamines in regulating immune function. The experments outlined will investigate the changes that occur to immune mechanisms as the result of CNS catecholamine depletion. Intracisternal (i.c.) injection of the catecholamine neuroleptic 6-hydroxydopamine (6-OHDA) impairs both the IgM and IgG primary humoral immune response. These experiments will examine the effects of 6-OHDA on T-cell, B-cell and macrophage function and their injections during the immune response. T-cells and B-cells from animals injected with 6-OHDA or saline (i.c.) will be mixed in various combinations to determine the effects of 6-OHDA on T-helper and B-cell function in an in vitro antibody response to sheep erythrocytes (SRBC). T-cell and B-cell function will also be determined by stimulating spleen cells from 6-OHDA and saline treated animals with the T-cell mitogen concanavalin A and the B-cell mitogen lipopolysaccharide. Preliminary data indicate that 6-OHDA impairs immune responsiveness by interfering with early events in the induction of the immune response. Therefore, the effects of 6-OHDA on splenic adherent cell antigen presentation and on the production of the lymphokines interleukin-1 (IL-1) and interleukin-2 (IL-2) will be determined. T-cells of various phenotypes and macrophages will be added to standard in vitro primary SRBC cultures to evaluate the induction of suppressor cells by 6-OHDA. Several reports indicate that intraventricular administration of 6-OHDA alters the release of pituitary hormones. Experiments using hypophysectomized mice injected with 6-OHDA i.c. will assess the role of these hormones as neural-immune communicating factors. Changes in the output of these hormones may be responsible for immune impairment following 6-OHDA treatment, either by increasing or decreasing hormone levels.
