No abstract

Interleukin (IL)-6 has been proposed to mediate several sickness responses, including brain-mediated neuroendocrine, temperature, and behavioral changes. However, the exact mechanisms and sites of action of IL-6 are still poorly understood. In the present study, we describe the effects of central administration of species-homologous recombinant rat IL-6 (rrIL-6) on the induction of hypothalamic-pituitary-adrenal (HPA) activity, fever, social investigatory behavior, and immobility. After intracerebroventricular administration of rrIL-6 (50 or 100 ng/rat), rats demonstrated HPA and febrile responses. In contrast, rrIL-6 alone did not induce changes in social investigatory and locomotor behavior at doses of up to 400 ng/rat. Coadministration of rrIL-6 (100 ng/rat) and rrIL-1β (40 ng/rat), which alone did not affect the behavioral responses, reduced social investigatory behavior and increased the duration of immobility. Compared with rhIL-6, intracerebroventricular administration of rrIL-6 (100 ng/rat) induced higher HPA responses and early-phase febrile responses. This is consistent with a higher potency of rrIL-6, compared with rhIL-6, in the murine B9 bioassay. We conclude that species-homologous rrIL-6 alone can act in the brain to induce HPA and febrile responses, whereas it only reduces social investigatory behavior and locomotor activity in the presence of IL-1β.

Peripheral administration of lipopolysaccharide (LPS) may activate the hypothalamus-pituitary-adrenal (HPA) axis by way of both neural and humoral mechanisms. We have investigated whether biologically active endotoxin appears in the general circulation after intraperitoneal administration of LPS (5 or 100 μg/kg) to rats and whether this is a prerequisite for activation of this HPA axis. Within 15 min, endotoxin appeared in the general circulation, whereas elevations of plasma adrenocorticotropic hormone (ACTH), corticosterone, and interleukin (IL)-6 concentrations were not detected until 90 min after LPS injection. At this time, a marked interindividual variation was observed in plasma concentrations of endotoxin, ACTH, corticosterone, and IL-6. Elevated levels of plasma endotoxin were associated with elevated levels of ACTH, corticosterone, and IL-6. Intravenous administration of the LPS antagonist cationic antimicrobial protein 18 (5 mg/kg), which did not affect cytokine production in the peritoneal cavity, markedly reduced plasma ACTH, corticosterone, and IL-6 levels after 5 μg/kg LPS. Our results suggest that circulating endotoxin is required for the activation of the HPA axis. They also favor a role for circulating IL-6 in this response.

No abstract

With the final aim of identifying the testicular steroids involved in the feedback mechanism of the hypothalamus-pituitary-gonad axis, steroid secretion by the testis of African catfish, Clarias gariepinus, was studied in vitro, by means of gas chromatography followed by mass spectrometry. Testicular fragments of sexually mature catfish raised in captivity were incubated in L-15 medium with and without catfish pituitary extract (cfPE). Without adding cfPE, 22 steroids could be identified, amongst which 11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketotestosterone and 11-ketoandrostenedione were dominating. After incubation in the presence of cfPE, the concentrations of the four 11-oxygenated steroids were increased about 4-fold. The amounts of pregnane derivatives in the incubation medium showed the largest increases in the presence of cfPE. 5β-Pregnane-triol levels, for example, were 60-fold higher than in the medium from control incubations. The secretion of 5α- and 5β-androstanes was also stimulated by cfPE.The stimulation was not equal for all steroids, indicating that cfPE not only stimulates total steroidogenesis by increasing the availability of cholesterol, but also by influencing specific steroid converting enzyme activities.