Injection Of Interleukin-1 Beta Research Articles

Intraperitoneal injections of prostaglandin E2 attenuate hyperthermia induced by restraint or interleukin‐1 in rats.

1. The purpose of this study was to investigate the effect of the intraperitoneal (I.P.), intravenous (I.V.) or intrapreoptic area (POA) injection of prostaglandin E2 (PGE2) on the body temperature of restrained and unrestrained rats. The effect of I.P. PGE2 on the body temperature of rats during fever induced by I.P. injection of interleukin-1 beta (IL-1 beta) was also investigated. 2. Prior to injection, restrained rats had body temperatures of approximately 1 degree C higher than unrestrained rats. The I.P. injection of PGE2 (0.05 and 0.5 mg kg-1) caused body temperature to fall towards the pre-restraint levels in a dose-dependent manner. This fall in body temperature was preceded by a sharp increase in tail skin temperature that was also dependent on dose. The I.P. injection of PGE2 had no effect on the body temperature of unrestrained animals. 3. The I.V. injection of PGE2 caused very little change in the body temperature of restrained rats. However, when injected I.V. into unrestrained animals, PGE2 caused dose-dependent fevers. The injection of PGE2 (50 ng) into the POA resulted in fever in both restrained and unrestrained animals. 4. The I.P. injection of IL-1 beta (10 micrograms kg-1) caused a biphasic fever that lasted at least 420 min. The I.P. injection of PGE2 180 min after the injection of IL-1 beta caused a transient decrease in the rats' body temperature. This drop in body temperature was not associated with a decrease in metabolic rate. 5. These data support the hypothesis that during restraint stress hyperthermia and IL-1 beta fever, the I.P. injection of PGE2 acts peripherally to lower the body temperature of rats.

Pro- and anti-inflammatory roles of interleukin-1 in recurrence of bacterial cell wall-induced arthritis in rats

A specific interleukin-1 (IL-1) receptor antagonist (IL-1ra) was used to examine the roles of IL-1 in an experimental model designed to analyze the reactivation phase of erosive arthritis, induced in rats with peptidoglycan-polysaccharide polymers (PG-APS) isolated from cell walls of group A streptococci. Monoarticular arthritis was initiated by injection of a small dose of PG-APS into an ankle joint, and reactivation was induced by intravenous injection of PG-APS 20 days later. Human recombinant IL-1ra given at a dose of 2 to 3 mg/kg at the time of reactivation of arthritis and at 6-h intervals inhibits the increase in joint swelling by at least 60%. Joint swelling is suppressed 30 to 50% when the initial treatment with IL-1ra is delayed until 6 h after reactivation. IL-1ra is not effective when the initial injection is delayed 12 or 24 h. With an injection schedule of IL-1ra given at the time of reactivation and every 6 h, treatment can be stopped at 24 h and the suppression of swelling is no different from that in rats for which injections are continued for 4 days. The results indicate that IL-1 has a prominent, although not exclusive, role in initiating inflammation in this model and is involved in the amplifying processes in progressive inflammation and chronic erosive disease. An anti-inflammatory function of IL-1 is also indicated from data showing that IL-1ra treatment limited to 6 h or less after the induction of reactivation enhances joint swelling, whereas intravenous injection of human recombinant IL-1 beta 24 h before reactivation suppresses the reactivation of arthritis.

Suppression of splenic macrophage interleukin-1 secretion following intracerebroventricular injection of interleukin-1β: Evidence for pituitary-adrenal and sympathetic control

Intracerebroventricular (ICV) injections of interleukin-1 beta (IL-1β) produced a dose-dependent increase in plasma corticosterone and adrenocorticotropic hormone (ACTH) within 2 hr of injection and then declined over the next 24 hr. Using a potent steroidogenic dose of IL-1β (5 ng), ICV injection resulted in suppression of splenic macrophage IL-1 secretion following stimulation by LPS in vitro. Macrophage TGF-β secretion was not affected, indicating a differential action of ICV IL-1β on macrophage cytokine production. Following adrenalectomy (ADX), the suppressive effect of ICV IL-1β was reversed and resulted in stimulation of macrophage IL-1 secretion, indicating that the suppression was mediated by adrenocorticol activation. However, surgical interruption of the splenic nerve to eliminate autonomic innervation of the spleen also prevented the macrophage suppressive signal in rats given ICV IL-1β. Furthermore, the combination of ADX and splenic nerve section resulted in a potent stimulatory effect of ICV IL-1β on splenic macrophage IL-1 secretion which was greater than either ADX or splenic nerve section alone. These results support the concept of a negative feedback on macrophage IL-1 secretion by the central action of IL-1β and indicate that both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system mediate this effect.

Interleukin-1 Inhibits the Ovarian Steroid-Induced Luteinizing Hormone Surge and Release of Hypothalamic Luteinizing Hormone-Releasing Hormone in Rats*

Interleukin-1 (IL-1), a polypeptide cytokine secreted by activated macrophages, has been postulated as a chemical messenger between the immune and endocrine systems. IL-1-immunopositive neurons and fibers have been visualized in the human and rat hypothalamus, and IL-1 receptors are present in the rat brain. We have examined the effects of human recombinant IL-1 (alpha- and beta-subtypes) on LH release in vivo and hypothalamic LHRH release in vitro. Ovariectomized rats were primed with estradiol benzoate, and progesterone was injected 48 h later to elicit a LH surge in the afternoon. IL-1 alpha and IL-1 beta were injected either intracerebroventricularly (icv) via a preimplanted cannula in the third ventricle of the brain or iv. Systemic injection of IL-1 alpha or IL-1 beta (58.8 pmol at 1300 and 1500 h) failed to influence the afternoon LH surge seen in saline-injected control rats. However, IL-1 beta (1.76 pmol) administered icv at 1300 and 1500 h or a single icv injection at 1300 h blocked the progesterone-induced LH surge. Similar icv injections of IL-1 alpha also significantly suppressed the afternoon LH surge compared to that in saline-injected control rats. However, IL-1 alpha was relatively less effective than the beta-subtype, since the LH surge was detected in some rats. To ascertain whether suppression of the LH surge was due to inhibition of LHRH release, the medial basal hypothalamus-preoptic area of estradiol benzoate-progesterone-treated ovariectomized rats was incubated with and without IL-1. Both IL-1 alpha and IL-1 beta, at concentrations of 0.1 nM and higher, significantly suppressed LHRH release in vitro from the medial basal hypothalamus-preoptic area. In contrast, IL-1 (10 nM) was completely ineffective in suppressing LHRH release from the microdissected median eminence. These results demonstrated an overall inhibitory effect of icv IL-1 on the LHRH-LH axis and suggest that suppression of the steroid-induced LH surge by IL-1 may primarily be due to inhibition of LHRH release at hypothalamic sites located within the blood-brain barrier.

Effects of peripheral administration of recombinant human Interleukin-1 beta on feeding behavior of the rat

This study was undertaken to investigate the changes in feeding behavior, including ambulatory activity, induced by a single injection of Interleukin-1 beta (IL-1) (2 ug/rat) at 18:00, just before the dark phase. For this purpose, we used the Gunma University-type automatic apparatus for continuous and direct measurement of ambulation and drinking. A significant decrease in food intake was observed for 12 hours after treatment with IL-1. Peripheral administration of IL-1 also produced a marked decrease in ambulatory activity within 3 hours which continued for 6 hours. In addition, IL-1 produced a marked decrease in drinking behavior during the first 6 hours. We reported here the changes in consummatory and ambulatory behavior of rats after acute administration of IL-1. The sickness which IL-1 produced may, at least in part, contribute to these phenomena, although precise mechanisms are still unknown.

Effect of interleukin-1 on adrenocortical activity in intact and hypothalamic deafferentated male rats

The present study was designed to elucidate the site of action of interleukin 1 (IL-1) modulation of the hypothalamic-hypophyseal-adrenal (HHA) axis. An intraperitoneal injection of recombinant human IL-1 beta (160 U/rat) significantly elevated serum levels of ACTH and corticosterone (CS). In rats with complete mediobasal hypothalamic deafferentation, the HHA response to IL-1 was inhibited. An intracerebroventricular injection of rIL-1 (2 U/rat) caused a marked increase in serum ACTH and CS. These results suggest that IL-1 activates the HHA axis by a direct effect upon the brain, and that intact neural connections between the mediobasal hypothalamus and extrahypothalamic brain regions are essential for IL-1-induced HHA responses.