Role of nitric oxide in the cerebrovascular and thermoregulatory response to interleukin-1 beta

Central administration of interleukin-1 beta (IL-1 beta) increases cerebral blood flow (CBF) and body temperature, in part, through the production of prostaglandins. In previous studies, the temporal relationship between thes e effects of IL-1 beta have not been measured. In this study, we hypothesiz ed that the increase in CBF occurs before any change in brain or body tempe rature and that the cerebrovascular and thermoregulatory effects of IL-1 be ta would be attenuated by inhibiting the production of nitric oxide (NO). A dult male rats received 100 ng intracerebroventricular (icv) injection of I L-1 beta, and cortical CBF (cCBF) was measured by laser- Doppler in the con tralateral cerebral cortex. A central injection of IL-1 beta caused a rapid increase in cCBF to 133 +/- 12% of baseline within 15 min and to an averag e of 137 +/- 12% for the remainder of the 3- h experiment. Brain and rectal temperature increased by 0.4 +/- 0.2 and 0.5 +/- 0.2 degrees C, but not un til 45 min after IL-1 beta administration. Pretreatment with N omega -nitro - L- arginine methyl ester (L- NAME; 5 mg/ kg iv) completely prevented the changes in cCBF and brain and rectal temperature induced by IL-1 beta. L-Ar ginine (150 mg/ kg iv) partially reversed the effects of L- NAME and result ed in increases in both cCBF and temperature. These findings suggest that t he vasodilatory effects of IL-1 beta in the cerebral vasculature are indepe ndent of temperature and that NO plays a major role in both the cerebrovasc ular and thermoregulatory effects of centrally administered IL-1 beta.