The antipyretic effect of AVP, α-MSH and ACTH consists in lowering the thrmoregulatory threshold and in shortening the time span of the fever. Thus, neuropeptides influence activity of hypothalamic neurones regulating body temperature. This was confirmed by recent experiments of Moravec (this volume) which indicate that spontaneous activity and thermosensitivity of neurones in hypothalamic slices can be influenced, by AVP. Why neuropeptides of different chemical structure such as AVT, on one hand, and α-MSH and ACTH, on the other hand, induce the same effect on thermoregulation remains to be elucidated.
Haloperidol when applied intraperitoneally to cold-exposed febrile rabbits induces a strong hypothermic effect. This effect is due to the downward shift of the threshold central temperature for induction of cold thermogenesis and vasomotion. The shift occurs during the early phase of the fever and is less prominent during the late phase of the fever. The hypothermic effect of high doses of haloperidol can eliminate the increase of body temperature in febrile individuals.
The study was designed to prove the hypothesis that lipopolysaccharide (LPS)-induced fever elicits the changes in surfactant specific proteins, potentially related to thermal tachypnea. In adult rats fever was induced by intraperitoneal administration of LPS at a dose 100 μg/kg of body weight; control group received saline. Respiratory parameters, arterial blood gases and pH and colonic body temperature (BT) were recorded. Five hours later, surfactant proteins (SP) A, B, C and D were evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue (LT). LPS evoked monophasic thermic response (at 300 min 38.7±0.2 vs. 36.4±0.3 °C, P<0.05) and an increase in minute ventilation due to changes in breathing rate and tidal volume. LPS-instilled animals had higher levels of SP-A and SP-D in LT (P<0.05 and 0.01), and higher SP-D in BALF (P<0.01) than controls. SP-B increased in LT and SP-C in BALF of animals with LPS (both P0.05 vs. controls). The changes in all surfactant specific proteins are present in LPS-induced fever. Alterations of proteins related to local immune mechanisms (SP-A, SP-D) are probably a part of general inflammatory response to pyrogen. Changes in proteins related to surface activity (SP-B and SP-C) might reflect the effort of the body to stabilize the lungs in thermal challenge., M. Kolomaznik, I. Zila, J. Kopincova, D. Mokra, A. Calkovska., and Obsahuje bibliografii
The effect of AVP on unit activity and temperature sensitivity was tested in hypothalamic slices of the rat. The results demonstrate that AH/PO neurones in vitro react to AVP by significant changes of both static discharge and temperature sensitivity supporting the idea of direct modulation of thermoregulatory neurones by AVP.
To specify the role of individual cytokines in the immune response to pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the experiments. Different pyrogens (lipopolysaccharide from Escherichia coli - LPS and live Borrelia afzelii) were applied and the time course of changes in concentrations of different cytokines in the medium was followed using the ELISA method. It was found that nonstimulated human PBMC proliferate under in vitro conditions and produce IL-6, TNF-a, IL-10 and finally also IL-1b. Productions of IL-12 and INF-g are not changed. Proliferation of PBMC is potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS increase the net production (stimulated minus unstimulated) of IL-1b and TNF-a significantly, while production of IL-6 was smaller. A delayed increase in the production of IL-10 was also observed. Productions of IL-12 and INF-g were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia, increases also the production of IL-12 and IFN-g, besides IL-1b, TNF-a, IL-6 and IL-10. Productions of IL-1b, IL-6 and TNFa increased immediately after incubation with both LPS and Borrelia, while productions of IL-12 and INF-g begin to increase 8 hours and production of IL-10 12 hours after stimulation. Data indicate that stimulation with different pyrogens may activate the cells of the immune cascade in a different way. Stimulation of BPMC by LPS seems to activate the initial steps of the immune response (macrophages and granulocytes) only, while infection with live Borrelia also stimulates the later phase of the immune response, probably due to effect of initially produced cytokines., L. Janský, P. Reymanová, J. Kopecký., and Obsahuje bibliografii
To specify the role of individual cytokines in the immune response to pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the experiments. Different pyrogens (lipopolysaccharide from Escherichia coli - LPS and live Borrelia afzelii) were applied and the time course of changes in concentrations of different cytokines in the medium was followed using the ELISA method. It was found that nonstimulated human PBMC proliferate under in vitro conditions and produce IL-6, TNF-a, IL-10 and finally also IL-1b. Productions of IL-12 and INF-g are not changed. Proliferation of PBMC is potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS increase the net production (stimulated minus unstimulated) of IL-1b and TNF-a significantly, while production of IL-6 was smaller. A delayed increase in the production of IL-10 was also observed. Productions of IL-12 and INF-g were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia, increases also the production of IL-12 and IFN-g, besides IL-1b, TNF-a, IL-6 and IL-10. Productions of IL-1b, IL-6 and TNFa increased immediately after incubation with both LPS and Borrelia, while productions of IL-12 and INF-g begin to increase 8 hours and production of IL-10 12 hours after stimulation. Data indicate that stimulation with different pyrogens may activate the cells of the immune cascade in a different way. Stimulation of BPMC by LPS seems to activate the initial steps of the immune response (macrophages and granulocytes) only, while infection with live Borrelia also stimulates the later phase of the immune response, probably due to effect of initially produced cytokines., L. Janský, P. Reymanová, J. Kopecký., and Obsahuje bibliografii
In rabbits and guinea pigs, hypothalamic sites for prostaglandin Ej (PGE2) action were studied by means of in vitro receptor autoradiography. The density of PGE2 binding sites (probably PGE2 receptors) was the highest in the anterior wall of the third ventricle (A3V). This result is consistent in all mammalian species ever studied, suggesting a fundamental role of the A3V in the hypothalamic action of PGE2, such as fever.
Fever developing after intracerebral injections of lipopolysaccharide (LPS) to guinea-pigs were monophasic, with only one peak of inner body temperature,slowly developing and longlasting in a dose range 20 to 200 ng of LPS. Latency time was inversely related to the dose of LPS. Indomethacin injected to the third brain ventricle did not abolish fever response.
Previous studies have substantiated the antipyretic role played by extrahypothalamic limbic system (EXHY-LS) AVP during fever. Repeated attempts to elucidate other thermoregulatory functions of this hormone have failed. Circumstantial evidence, however, suggest central role for this hormone in thermoregulation under hypohydration. Hypohydration, hyperosmolarity and hypovolaemia induce upward shifts in temperature thresholds for activation of heat dissipating mechanisms. When hypovolaemia is superimposed on hyperosmolarity these shifts are additive. Analogously, these two stressors when combined, decrease the osmotic threshold for AVP release. In rats, the elevated temperature thresholds for evaporative cooling and peripheral vasodilation occurring with hypohydration are positively correlated with lower Hypothalamic/EXHY-LS AVP ratio. Reciprocal relations between limbic system and blood AVP contents suggest competitive interaction between central and peripheral demands. Hypothesis for the possible mode of action of central AVP in thermoregulation under hypohydration is discussed.