The long term goal is to determine the effects of the neurohormones Beta endorphin and met-enkephalin on human immune cell function. This study will utilize isolated human neutrophils (PMN), monocytes, and lymphocyte subsets to achieve this goal.
The first aim i s to determine if pokeweed mitogen stimulated IgG and IgM production by B cells is suppressed by Beta endorphin and met-enkephalin. Studies will determine if altered responses are due to induction of helper or suppressor T cells or a direct effect on B cells. Opiate peptide modulation of T cell dependent and independent antibody production and effects on primary and secondary immune responses in vitro will be investigated using hemolytic plaque assays.
The second aim i s to determine if Beta endorphin or met-enkephalin modulate lymphokine production by T cells. Four lymphokine activities will be studied (including Interleukin 2, Lambda interferon, T lymphocyte chemotactic factor, and monocyte differentiating activity). These studies will provide information pertinent to opiate peptide effects on the initiation of an immune response, the expression of cellular immunity, and the maturation of effector cells.
The third aim i s to determine if opiate peptides affect the expression of immunity by modifying the adherence of human PMN, monocytes, and lymphocytes. Adherence is essential to leukocyte binding to the vascular endothelium before migration into tissues. Adherence to serum coated slides will be quantitated for each cell type and effects of opiate peptides will be related to their action on cell locomotion.
The fourth aim i s to study the binding of radiolabeled Beta endorphin, met-enkephalin, and naloxone to human PMN, monocytes, and lymphocytes. These studies will provide direct evidence for the interaction of opiate peptides with each cell type. These studies will also determine if multiple opiate receptors are present on normal human leukocytes and if naloxone inhibitible and non-inhibitible receptors are present. The fifth aim is to analyze the structural requirements necessary for activity and binding of opiate peptides using endorphin fragments and met-enkephalin analogs. This proposal provides a comprehensive study of opiate peptide effects on the human immune cell system. Comparative studies of individual and cooperative functions of these cells will provide a basis to assess opiate peptides in immunoregulation. Binding studies will support the functional data obtained with individual cells and help to define the complex relationship of opiate peptides, immunity, and immunosuppression during stress-induced elevation of endorphins.
