Antipyretic actions of human recombinant lipocortin‐1

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Abstract
The effect of human recombinant lipocortin‐1 (hrLC‐1) on the pyrogenic actions of the synthetic polyribonucleotide polyinosinic: polycytidylic acid (poly I: C) has been studied in conscious rabbits. Poly I: C (2.5 μg kg−1) given i.v. produced a biphasic fever with a first peak after 90–105 min and a second peak between 225–240 min. hrLC‐1 (50 μg kg−1) given i.v. simultaneously with the poly I: C produced a significant reduction in the febrile response but without complete suppression. The thermal response index over 5 h (TRI5) was 4.69 ± 0.51 for poly I: C given with saline and the TRI5 for poly I: C given with hrLC‐1 was 2.66 ± 0.45 (values are for n = 5 ± s.e.mean, P < 0.05). hrLC‐1 administered alone had no effect on body temperature and its antipyretic activity was lost on heating. In a separate series of experiments 1 h pretreatment with dexamethasone (1 mg kg−1) given i.v. reduced the pyrogenic response (TRI5) to poly I: C (2.5 μg kg−1) from 4.87 ± 0.54 without dexamethasone to 2.00 ± 0.25 (n = 5, P < 0.05) and dexamethasone given alone had no effect on body temperature. These data demonstrate that LC‐1 possesses antipyretic actions and raises the possibility that the antipyretic actions of dexamethasone are mediated through the induction of LC‐1.