Tuftsin-phosphorylcholine attenuate experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) which carries a significant burden of morbidity and mortality. Herein we examine the effects of acute treatment with tuftsin-phosphorylcholine (TPC), a novel immune-modulating helminth derived compound, on a murine model of MS. Experimental autoimmune encephalomyelitis (EAE) mice received acute treatment with TPC showed an improved clinical score and significantly less signs of inflammation and demyelination in CNS tissue compared with vehicle treated EAE mice. Our findings suggest that TPC may provide a beneficial clinical effect in EAE and may therefore have a potential value for ameliorating clinical manifestations and delaying disease progression in MS.

Changes in immunoreactivity of orexin-A-positive neurons after intravenous lipopolysaccharide injection.

BACKGROUND: Orexins are neuromediators that help regulate many different physiological processes; however, their role in regulating immune system functioning is unclear. This study sought to investigate the distribution of orexin in hypothalamic orexin-containing neurons during the first 6 hours after an intravenous injection of a lipopolysaccharide. MATERIAL/METHODS: Orexin-containing neurons were detected by immunohistochemistry (avidin-biotin) on frontal sections from the brains of intact rats and rats after injections of either saline or lipopolysaccharide. RESULTS: Analysis of immunohistochemically stained sections (levels 26-32 according to Swanson's atlas) revealed that the main pool of orexin-containing neurons was located at brain levels 28 to 30. No changes were shown in the number of orexin-containing neurons in the hypothalamus of intact animals at different times of a day. Visualization of orexin-containing neurons in the lateral hypothalamus decreased only in 6 hours after an injection of lipopolysaccharide (500 microg/kg body weight) at levels 28, 29, and 30 of the rat brain; this might have been the result of changes in the balance of orexin synthesis and utilization. CONCLUSIONS: These data suggest that orexin-containing neurons play a role in complex reactions in the brain to lipopolysaccharide application.

Natural killer cell cytotoxic activity and c-Fos protein synthesis in rat hypothalamic cells after painful electric stimulation of the hind limbs and EHF irradiation of the skin.

BACKGROUND: The goal was to assess changes in natural killer (NK) cell activity and the number of c-Fos-positive cells in hypothalamic structures induced by painful electrical stimulation and to use extremely high-frequency (EHF) irradiation of the skin to modulate these processes. MATERIAL/METHODS: Experiments were performed on Wistar rats subjected to painful electrical stimulation of the hind limbs combined with EHF irradiation of the skin. The cytotoxic activity of splenic NK cells was assessed by their ability to lyse K-562 tumor cells in vitro. c-Fos-like protein was detected by an immunoperoxidase technique. RESULTS: Painful electric stimulation was associated with a significant decrease in splenic NK cytotoxicity and a dramatic increase in c-Fos-positive cell counts in some hypothalamic structures, particularly in the anterior hypothalamic nucleus (AHN) and the perifornical lateral hypothalamic area (LHA). Two EHF exposures, one before and one after electric stimulation, prevented the suppression of splenic NK cell activity and caused a decrease in the number of c-Fos-positive cells expressed in the ventromedial hypothalamic nucleus (VMH) and basal LHA. Negative correlation was shown between c-Fos-positive cell counts in the AHN and LHA and the cytotoxic activity of NK cells. CONCLUSIONS: These results suggest that painful electric stimulation of the hind limbs of rats causes a reorganization of the central mechanisms that regulate splenic NK cell activity, resulting in a decrease in their cytotoxicity, and that EHF irradiation of the skin prevents this reorganization, thus protecting splenic NK cell activity from the impairment induced by this stressor.

Effect of epitalon on interleukin-1beta signal transduction and the reaction of thymocyte blast transformation under stress.

OBJECTIVES: The aim of this research consisted in studying the effects of tetrapeptide Epitalon on both thymocyte proliferation and interleukin-1beta (IL-1beta) signal transduction via sphingomyelin pathway in the cerebral cortex membranes of mice exposed to stresses exerting diverse effects upon humoral immune response. DESIGN AND SETTING: The experiments were performed on male (CBAxC(57)BL(6))F1 mice aged 8 10 weeks. Two models of experimental stress were used: immune-stimulatory rotation stress and immune-suppressive combined stress (cooling followed by immobilization). The concomitant effect of Epitalon was determined according to its influence on thymocyte proliferation stimulated by concanavalin A at a sub-optimal dose and recombinant IL-1beta. The activity of membrane neutral sphingomyelinase (nSMase), the key enzyme of the sphingomyelin signal transduction pathway, was assayed according to modified Rao and Spence's method (1976). RESULTS: The investigation demonstrated that Epitalon increased thymocyte proliferative activity, both enhanced under rotation stress and suppressed under combined one. It also increased IL-1beta concomitant effect. These findings corresponded to Epitalon effect on diverse stress-induced changes in nSMase activity in cerebral cortex fraction P2. Epitalon activated nSMase in the cerebral cortex membranes of intact mice and increased IL-1beta stimulatory effect on the enzyme activity. CONCLUSIONS: The obtained results provided a conclusive evidence of Epitalon stress-protective effect at the level of IL-1beta signal transduction via sphingomyelin pathway in the nerve tissue, as well as at the level of target thymocyte proliferation.

C-fos gene expression induced in cells in specific hypothalamic structures by noxious mechanical stimulation and its [correction of it's] modification by exposure of the skin to extremely high frequency irradiation.

OBJECTIVES: The purpose of this study was to determine: 1) The spatial pattern of c-fos gene expression in rat hypothalamic neurons after exposure to NMS and 2) The expression of c-fos gene after combined exposure to NMS and EHF irradiation of the rat skin. METHODS: The experiments were performed on 28 male adult Sprague-Dawley rats. After rats were subjected to noxious mechanical stimulation (NMS) or its combination with EHF irradiation of the skin, cells in various hypothalamic structures were analyzed to determine theirs effects on c-fos gene expression, an accepted marker of the activation of neurons. C-Fos-like protein was revealed by an indirect immunoperoxidase method. RESULTS: This study revealed that NMS stimulates c-fos gene expression in the anterior hypothalamic nucleus (AHN), dorsomedial hypothalamic nucleus (DMH), ventromedial hypothalamic nucleus (VMH), and lateral hypothalamic area (LHA) by 157, 101, 199 and 115% respectively compared to control animals. Combined exposure to NMS and EHF irradiation directed at the skin in the region of the St36 acupuncture point projection site (left side) results in a decrease of the number of neurons that are activated in the AHN, DMH, VMH, and LHA by 33.6, 13.2, 31.0 and 32.9% respectively compared to the number of neurons activated by exposure to NMS by itself. EHF exposure of the skin of rats not subjected to NMS differentially effects the number of c-Fos positive cells expressed in hypothalamic structures: a decrease of 39.7% was observed in the number of activated neurons in the central part of LHA (level 28) compared to sham-irradiated animals, while an increase of 80.95% was noted in the number of c-Fos positive cells in the DMH compared to sham-irradiated animals. CONCLUSIONS: The spatial pattern and degree of activation of c-fos gene expression has been shown in cells of the hypothalamus of rats after exposure to NMS by itself and after NMS combined with EHF irradiation of the skin. The "stress" reaction of cells in specific hypothalamic structures has been shown to be decreased after EHF exposure of the skin.

Contemporary Topics in Neuroimmunomodulation.

The investigational subject of immunophysiology (neuroimmunomodulation, psychoneurophysiology) is known to be the studies of interactions between nervous and immune systems in normal and pathological conditions on different structural levels of interactions between these systems. It has been shown that expression of genes of immediate (c-fos) and rapid (IL-2) reactions in response to stimuli of non-immune nature occurs not only in lymphoid cells, but also in certain structures of central nervous system. In addition, there are many facts, demonstrating the elevation of IL-1 production by cells of monocyte-macrophage system and the expression of IL-1 genes in brain after action of irritants of different origin. The IL-1 level is revealed to be increased after action of different stress factors that can be predictable. The studies are started having concern with rather new and extremely important aspect of immunophysiology, that is the studies of cytokine expression in brain and its role in brain function. Now it is already clear that practically all the spectrum of cytokines is present in brain and many of them, including IL-1 and IL-2, are expressed not only on glial cells, but on neurons. Partly cytokine involvement is shown during the development of regulatory processes. For example, IL-1 and IL-2 stimulate production of corticotropin releasing and lutein stimulating factors. It is possible to suggest that this line of studies would be highly perspective either for immunology, or for physiology of XXI century.