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-1 beta (rIL-1 beta) or recombinant tumour necrosis factor alpha (rTNF alpha) 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 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 E2 (PGE2) production in vitro. Since serum amyloid A did not affect body temperature or hypothalamic 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.