Hepatic acute-phase reaction in histamine-deficient gene targeted mice.

Histamine is a versatile mediator that, according to in vitro studies, affects the synthesis of inflammatory cytokines and acute-phase proteins. The histidine-decarboxylase knockout (HDC-/-) mouse is a model of in vivo investigation of the physiologic and metabolic integration of the acutephase response. These mice do not synthesise histamine and feeding them with histamine-poor diet they are almost completely histamine-deficient. We compared the serum concentrations of representatives of acute-phase plasma proteins, as well as the levels IL-6 and IL-1alpha in wild type and HDC-/- mice during local (turpentine-induced) or systemic (LPS-induced) inflammation. The level of some acute-phase proteins significantly differed in wild-type and HDC-/- mice while others remained unaffected. The IL-6 levels are also differ in the wild-type and histamine-deficient animals, suggesting that the effect of histamine is attained through IL-6, although direct effect is not disclosed yet.