Neurophysiological and endocrine consequences of immune activity.

The studies presented herein demonstrate the potency with which activity of the immune system is able to influence the central nervous system. Electrophysiological recordings have demonstrated significant changes in preoptic area/anterior hypothalamic (PO/AH) multiunit electrical activity (MUA) following sensitization with sheep red blood cells. The peak of activity occurred on the fifth day after immunization, the same day that serum antibodies were first detected. A significant increase in paraventricular nucleus MUA was also demonstrated, but this appeared to be delayed with respect to that in the PO/AH, occurring on the sixth day. Further changes thought to be associated with the immune response also were found: Serum corticosterone levels were elevated on the eighth day of the response, and PO/AH tissue levels of norepinephrine were reduced between the sixth and tenth days. During induction of a secondary response, PO/AH MUA showed a different profile of activity from that recorded during the first response. Chronic administration of the immunosuppressive drug, cyclophosphamide, prevented the recorded changes in PO/AH MUA. These results suggest that some secretory product(s) of the activated immune system may be able to exert effects on the central nervous system. Various immunoactive substances therefore were administered intra-cerebroventricularly in order to examine their effects upon PO/AH MUA, cortical EEG and adrenocortical hormone secretory activity. alpha-Interferon and thymic humoral factor were both found to decrease PO/AH MUA, increase EEG synchronization, and decrease basal levels of circulating corticosterone. In contrast, histamine and interleukin-1 did not alter PO/AH MUA but did cause decreased EEG synchronization and increased serum corticosterone levels. With another preparation, a specific activating effect of interleukin-1 upon putative corticotropin-releasing factor-secreting neurones has also been found, identified vasopressinergic neurones not being affected.