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.