Inhibition of central actions of cytokines on fever and thermogenesis by lipocortin-1 involves CRF

In the present studies, the mechanisms underlying the inhibitory actions of lipocortin-1 on the pyrogenic and thermogenic properties of cytokines were investigated. Central (icv) injection of corticotropin-releasing factor (CRF, 4.7 μg) or the recombinant cytokines interleukin (IL)-1α (50 ng), IL-1β (5 ng), IL-6 (20 ng), IL-8 (20 ng), or tumor necrosis factor-α (TNF-α, 1 μg) in conscious rats produced significant increases in resting oxygen consumption (V̇O2, 13-26%) and colonic temperature (0.7-1.6°C) within 2 h postinjection. Administration (icv) of a recombinant fragment (NH2-terminus, 1-188 amino acids) of human lipocortin-1 (1.2 μg) produced small increases in V̇O2 (