Acute Phase Protein, Serum Amyloid A, Inhibits IL‐1‐ and TNF‐Induced Fever and Hypothalamic PGE₂ in Mice

The effect of serum amyloid A(SAA)on fever induced by recombinant interleukin‐1b(ril‐1β) or recombinant tumour necrosis factor α (rTNFα) was studied in mice. Serum amyloid A is an acute phase protein whose rise in pathological events is induced by the cytokines IL‐1. IL‐6 and TNF. Administration of human serum amyloid A to mice inhibited fever induced by rlL‐1β or TNFα in vivo, while the addition of human serum amyloid A lo mice hypothalamic slices inhibited IL‐1β or TNPα‐induced prostaglandin E₂ (PGE₂) production in vitro. Since serum amyloid A did not affect body temperature or hypothalmic PGE₂ levels when administered alone, it may represent a specific servo‐mechanism for fever regulation in acute events, and it suggests, for the first time, a possible feedback relationship between serum amyloid A and the immunoregulatory cytokines.