Acute phase protein, serum amyloid A, inhibits IL-1- and TNF-induced fever and hypothalamic PGE sub(2) in mice

The effect of serum amyloid A (SAA) on fever induced by recombinant interleukin-1 beta (rIL-1 beta ) or recombinant tumour necrosis factor alpha (rTNF alpha ) was studied in mice. Administration of human serum amyloid A to mice inhibited fever induced by rIL-1 beta or rTNF alpha in vivo, while the addition of human serum amyloid A to mice hypothalamic slices inhibited IL-1 beta - or TNF alpha -induced prostaglandin E sub(2) (PGE sub(2)) production in vitro. Since serum amyloid A did not affect body temperature or hypothalmic PGE sub(2) 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.