Modulation of innate immune functions by intracerebroventricularly applied neuropeptide Y: dose and time dependent...

Centrally applied neuropeptide Y (NPY) interacts with the autonomic nervous system and the hypothalamo-pituitary-adrenal (HPA) axis activity. Since these physiological systems have been shown to modulate innate immune functions, the effects of intracerebroventricular (i.c.v.) NPY administration on leukocyte subsets in the blood, spleen and intravascular pool of the lung, blood granulocyte chemiluminescence response, and splenic natural killer (NK) cell-mediated lysis were studied in Lewis rats. Concentration-dependent NPY effects were tested at 15 min and 24 h post i.c.v. injection at dosages of 10(-6) M, 10(-9) M, and 10(-12) M. Time dependent effects were investigated at 15 min, 1 h and 24 h after i.c.v. administration of 10(-9) M NPY. Compared to saline controls, an increased number of granulocytes and NK cells in the blood, associated with a decreased granulocyte function and NK cytotoxicity was observed 15 min following NPY infusion. This initial immunosuppression was followed by long lasting stimulatory effects of NPY on the functional capacity of both cell populations when tested at 1 h and 24 h. The dosage of i.c.v. 10(-6) M NPY produced no changes, whilst 10(-9) M produced maximal, and 10(-12) M still significant effects. Results provide evidence that centrally applied NPY influences innate immunity in a dose and time dependent fashion. Cell mobilization from the vascular marginal pool is likely to be an underlying mechanism for the initial immunosuppression.