We have continued to explore the relationship between somatostatin and affective - illness by performing somatostatin assays of human CSF and rat brain. Additionally, studies to elucidate the mechanisms of interleukin-2-induced neurotoxicity have also been undertaken in animals. A) Somatostatin - In addition to expansion of early studies of CSF somatostatin in patients with Alzheimer's disease, elderly depressed patients, and patients with eating disorders, we have identified a significant relationship between CSF somatostatin and CSF CRH in a variety of clinical populations. The apparent physiological relationship between the hypothalamic-pituitary-adrenal and somatostatin systems is further suggested by our observation of significant decreases in CSF somatostatin in normal volunteers during high-dose prednisone administration. Examination of brain somatostatin one hour following electroshock, and spinal cord somatostatin three days following unilateral pedal formalin administration in rats, revealed no significant alterations as a function of these procedures. However, the development of amygdala kindling in rats appears associated with altered processing of somatostatin M-RNA. Attempts to replicate and clarify the significance of these findings are currently underway. B) Interleukin-2 - In addition to demonstrating interleukin-2-induced behavioral alterations in rats, we have preliminary evidence suggesting that a blood-brain-barrier disturbance in the form of increased permeability of large proteins does not occur as a consequence of interleukin-2 administration. The mechanism of lymphokine-induced neurotoxicity is of great interest and is actively being explored.
