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Staphylococcal enterotoxin B induces fever, brain c-Fos expression, and serum corticosterone in rats. Am J Physiol Regulatory Integrative Comp Physiol 280: R1434-R1439, 2001.--The paraventricular nucleus of the hypothalamus (PVH) occupies a pivotal point within the network of brain nuclei coordinating critical host-defense responses. In mice, T cell-dependent immune stimuli, including the bacterial superantigen staphylococcal enterotoxin B (SEB), can activate the PVH. To determine whether T cell-dependent immune stimuli activate the PVH in rats, we assessed plasma corticosterone (Cort) levels, fever responses, and c-Fos expression in the PVH in animals treated with intraperitoneal injections of SEB. In animals with previously implanted abdominal thermisters, intraperitoneal injection of 1 mg/kg SEB resulted in a significant rise in body temperature, with a latency of 3.5-4 h. In separate animals, intraperitoneal injection of 1 mg/kg SEB resulted in a significant elevation of plasma Cort and induced c-Fos expression in parvocellular neurons within the PVH. These results support the idea that T cell-dependent immune stimuli activate brain pathways mediating host-defense responses such as fever and neuroendocrine changes. superantigen; thermoregulation; paraventricular hypothalamus; immediate-early gene

Hansen, Michael K., Kevin A. O'Connor, Lisa E. Goehler, Linda R. Watkins, and Steven F. Maier. The contribution of the vagus nerve in interleukin-1[Beta]-induced fever is dependent on dose. Am J Physiol Regulatory Integrarive Comp Physiol 280: R929-R934, 2001.--It has been suggested that proinflammatory cytokines communicate to the brain via a neural pathway involving activation of vagal afferents by interleukin-1[Beta] (IL-1[Beta]), in addition to blood-borne routes. In support, subdiaphragmatic vagotomy blocks IL-1[Beta]-induced, brain-mediated responses such as fever. However, vagotomy has also been reported to be ineffective. Neural signaling would be expected to be especially important at low doses of cytokine, when local actions could occur, but only very small quantities of cytokine would become systemic. Here, we examined core body temperature after intraperitoneal injections of three doses of recombinat human IL-1[Beta] (rh-IL-1[Beta]). Subdiaphragmatic vagotomy completely blocked the fever produced by 0.1 [micro]g/kg, only partially blocked the fever produced by 0.5 [micro]g/kg, and had no effect at all on the fever that followed 1.0 [micro]/kg rh-IL-1[Beta]. Blood levels of rh-IL-1[Beta] did not become greater than normal basal levels of endogenous rat IL-[Beta] until the 0.5-[micro]g/kg dose nor was IL-[Beta] induced in the pituitary until this dose. These results suggest that low doses of intraperitoneal IL-1[Beta] induce fever via a vagal route and that dose may account for some of the discrepancies in the literature. cytokines; vagotomy; immune-to-brain communication; rat

Hansen, Michael K., Kien T. Nguyen, Monika Fleshner, Lisa E. Goehler, Ron P. A. Gaykema, Steven F. Maier, and Linda R. Watkins. Effects of vagotomy on serum endotoxin, cytokines, and corticosterone after intraperitoneal lipopolysaccharide. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278: R331-R336, 2000.--The vagus nerve appears to play a role in communicating cytokine signals to the central nervous system, but the exact extent of its involvement in cytokine-to-brain communication remains controversial. Recently, subdiaphragmatic vagotomy was shown to increase bacterial translocation across the gut barrier and thus may cause endotoxin tolerance. The current experiment tested whether or not vagotomized animals have similar systemic responses to endotoxin challenge as do sham-operated animals. Subdiaphragmatically vagotomized and sham-operated animals were injected intraperitoneally with one of three doses (10, 50, 100 [micro]g/kg) of lipopolyssacharide (LPS) or vehicle, and blood samples were taken at 15, 30, 60, 90, and 120 min after the injection. The intraperitoneal injection of LPS increased circulating LPS levels at a]l time points examined. In addition, all three doses of LPS significantly increased serum interleukin (IL)-1[Beta], IL-6, and corticosterone in both control and vagotomized rats. In conclusion, vagotomy itself has no marked effect on circulating endotoxin levels or the production of IL-1[Beta], IL-6, or corticosterone in blood after an intraperitoneal injection of LPS. interleukin-1[Beta]; interleukin-6; vagus nerve; cytokine-to-brain communication

The possibility that immunological changes might contribute to symptom severity in fibromyalgia (FM) prompted this proof‐of‐concept study to determine whether differences in monocyte subpopulations might be present in persons with FM compared with healthy controls. Relationships were assessed by comparing specific symptoms in those with FM (n = 20) and patterns of monocyte subpopulations with healthy age‐matched and gender‐matched controls (n = 20). Within the same time frame, all participants provided a blood sample and completed measures related to pain, fatigue, sleep disturbances, perceived stress, positive and negative affect and depressed mood (and the Fibromyalgia Impact Questionnaire for those with FM). Monocyte subpopulations were assessed using flow cytometry. No differences were observed in total percentages of circulating monocytes between the groups; however, pain was inversely correlated with percentages of circulating classical (r = −0.568, p = 0.011) and intermediate (r = −0.511, p = 0.025) monocytes in the FM group. Stress and pain were highly correlated (r = 0.608, p = 0.004) in the FM group. The emerging pattern of changes in the percentages of circulating monocyte subpopulations concomitant with higher ratings of perceived pain and the correlation between stress and pain found in the FM group warrant further investigation. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]