CYTOKINES AND THERMOREGULATION - INTERLEUKIN-9 INJECTED IN PREOPTIC AREA FAILS TO EVOKE FEVER IN RATS

A number of the members of the family of cytokines including IL-1, IL- 2, IL-6, and IL-11 act directly in the brain to induce a febrile respo nse in the rat and other species. The purpose of this study was to exa mine the effect of interleukin-9 (IL-9) when this cytokine is applied directly to the thermosensitive and pyrogen reactive region of the ant erior hypothalamic, preoptic area (AH/POA). In male Sprague-Dawley rat s, guide cannulae for microinjection into the AH/POA were implanted st ereotaxically, and radio transmitters for monitoring body temperature (T-b) were placed intraperitoneally. Following postoperative recovery, recombinant murine macrophage inflammatory protein (MIP)-1 beta was m icroinjected in the AH/POA of each rat in a dose of 28 pg/mu l to iden tify pyrogen reactive sites in the AH/POA. Then recombinant human IL-9 was suspended in pyrogen-free CSF vehicle and microinjected in the sa me sites in concentrations of 2.4, 24, and 240 U/mu l. In contrast to the pyrexic action of MIP-1 beta, IL-9 failed to elicit a significant alteration in the T-b of the rats at any of the doses tested. IL-9 was also without effect on the intakes of either water or food. These res ults demonstrate that IL-9 applied to the region of the diencephalon i n which other cytokines act to evoke fever may not play a direct role in the thermogenic component underlying the acute phase response. Howe ver, as demonstrated in several different cell systems, IL-9 may requi re a cofactor related to pyrogen fora febrile response to develop.