Research Report Homeostatic alterations induced by interleukin-1b microinjection into the orbitofrontal cortex in the rat Bala ´zs Luka ´ts, Ro ´bert Egyed, La ´szlo ´ Le ´na ´rd, Zolta ´n Kara ´di * Institute of Physiology and Neurophysiology Research Group of the Hungarian Academy of Sciences, Pe ´cs University, Medical School, Pe ´cs, Szigeti u ´t 12, H-7624, Hungary Received 27 December 2004; revised 9 February 2005; accepted 29 March 2005 Abstract The present experiments were designed to elucidate the effect of direct orbitofrontal cortical administration of interleukin-1b (IL-1b) on the homeostatic regulation. Short- and long-term food intakes (FI), water intakes and body temperature (BT) were measured before and after a bilateral microinjection of IL-1b (with or without paracetamol /P/ pretreatment) into the orbitofrontal cortex (OBF) of Wistar rats, and the effects were compared with those found in vehicle-treated and i.p. injected IL-1b, IL-1bCP or control animals. In addition, blood glucose levels (BGLs), along a glucose tolerance test, and plasma concentrations of insulin, leptin, cholesterol, triglycerides and urate were determined in cytokine treated and control rats. Short-term FI was suppressed after orbitofrontal cortical or peripheral application of IL-1b. In the long-term FI, however, there was no significant difference among the groups. Cytokine microinjection into the OBF, similar to the i.p. administration, was also followed by a significant increase in BT. Pretreatment with P failed to influence the anorexigenic and hyperthermic effects of the centrally administered IL-1b. The sugar load led to a diabetes-like prolonged elevation of BGL in the IL-1b treated animals. Following cytokine administration, plasma levels of insulin and that of triglycerides were found decreased, whereas that of uric acid increased. The present findings confirm that the OBF is one of the neural routes through which IL-1b exerts modulatory effect on the central homeostatic regulation. q 2005 Elsevier Ltd. All rights reserved. Keywords: Food- and water intake; Body temperature; Glucose tolerance test; Metabolic measurements; Ventrolateral prefrontal cortex Introduction A constant, stable condition of the internal environment, the maintenance of homeostasis is of primary significance for the integrity of higher order living organisms. Various adaptive and defense mechanisms serve this function, and the so-called immunoregulators—the front-line of the cytokines—have important roles in it. The interleukin-1 (IL-1) group is one of the major representatives of the cytokines, and of its two ‘iso’forms (a and b), the beta form appears to be biologically more important in rodents and primates as well (Dinarello, 1996). This multifunctional cytokine is known to act as a mediator of the ‘acute phase response’ and it takes part not only in immunological but in several homeostatic processes as well (Dinarello, 1996; Plata-Salaman, 1991). It has already been reported to cause somnolence, elevation of body temperature and reduction of food intake (also known as symptoms of the so-called ‘sickness behavior’) after peripheral administration in various species (Dascombe, Rothwell, Sagay, & Stock, 1989; Hart, 1988; Montkowski, Landgraf, Yassouridis, Holsboer, & Schobitz, 1997; Plata-Salaman, 1989, 1991; Pu, Anisman, & Merali, 2000). In order to exert these effects, IL-1b is supposed to interact with the nervous system. Its synthesis has already been demonstrated ubiquitously in the periphery. Little is known, however, about its existence and function in the CNS. Microglial cells, astrocytes and even neurons themselves appear to possess IL-1 receptors and express this primary cytokine in broad areas (from the medulla up to the prefrontal-orbitofrontal cortical regions) along the whole rostrocaudal axis of the CNS (Bandtlow et al., 1990; Breder, Dinarello, & Saper, 1988; Farrar, Kilian, Appetite 45 (2005) 137–147 www.elsevier.com/locate/appet 0195-6663/$ - see front matter q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.appet.2005.03.014 * Corresponding author. E-mail address: zoltan.karadi@aok.pte.hu (Z. Kara ´di).