Characteristics of fever and acute-phase response induced in rabbits by IL-1 and TNF.

We investigated the effect of human recombinant interleukin 1 alpha (hrIL-1 alpha) and human recombinant tumor necrosis factor (hrTNF) on body temperature and acute-phase response, including changes in the plasma concentration of iron, zinc, and copper and in circulating leukocyte count. The intravenous injection of a smaller dose of either hrIL-1 alpha (0.5 micrograms/kg) or hrTNF (2 micrograms/kg) produced a monophasic fever, whereas a larger dose (hrIL-1 alpha, 2 micrograms/kg; hrTNF, 10 micrograms/kg) produced a biphasic fever. The intracerebroventricular injection of hrIL-1 alpha or hrTNF produced a dose-dependent fever. The intravenous injection of either hrIL-1 alpha or hrTNF decreased the plasma concentration of iron and zinc and increased the plasma copper concentration and the circulating leukocyte count. The intracerebroventricular injection of hrIL-1 alpha induced those responses, although the intracerebroventricular injection of hrTNF did not. The present results show that two kinds of monokines, hrIL-1 alpha and hrTNF, are intrinsically pyrogenic and induce the acute-phase response. Furthermore, it is suggested that hrIL-1 alpha induces febrile and acute-phase responses through its action on both the peripheral target organs and the central nervous system. However, hrTNF induces those responses only by its action on the peripheral target organs outside the blood-brain barrier.