Research "recover from illness defense complex" helper T cell immune mechanisms based on the "Fuxie" theory clearing away heat evil thoroughly nourishing kidney treatment of recurrent blood-heat syndrome Psoriasis.

INTRODUCTION: Psoriasis vulgaris (PV) is a chronic, painful, disfiguring, and disabling dermatological disease, which affects the physical and mental health of patients and impacts their quality of life. Current conventional systemic therapies can be costly, present risks of side effects, have limited efficacy and commonly recur following treatment cessation. Some Chinese herbal medicine therapies have shown therapeutic benefits for psoriasis vulgaris, including relieving symptoms and improving quality of life, and a potential of reducing relapse rate. However, explicit evidence has not yet been obtained. METHODS AND ANALYSIS: This is a pilot randomized controlled trial with the objective of investigating the effect of Jia Wei Liang Xue Xiao Feng San granules on relapse rate of recurrent PV and the correlation between Psoriasis area severity index (PASI) and key psoriasis-related cytokine changes and the number of cells. A total of 102 participants were recruited for this study, including 72 patients with recurrent PV, 15 healthy volunteers and 15 patients with psoriasis vulgaris who have recovered for more than 1 year. A total of 72 patients, with recurrent PV, will be randomized (1:1) to receive the oral Chinese herbal medicine Jia Wei Liang Xue Xiao Feng San or the oral Acitretin Capsule treatments for a period of 8 weeks. After this period, participants whose PASI scores improvement reached more than 75%, will undergo a 52-week follow-up phase.The primary outcome measures are as follows:The secondary study outcomes will include:This trial may provide a novel regimen for recurrent PV patients if the granules decrease recurrence rate without further adverse effects. ETHICS AND DISSEMINATION: The ethics approval was provided by the Sichuan Traditional Chinese medicine regional ethics review committee. The ethics approval number is 2018KL-055. The design and the results of the study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1900022766).

Danaparoid sodium attenuates the effects of heat stress.

BACKGROUND: Heat stroke is a condition characterized by high body temperature that can lead to hemorrhage and necrosis in multiple organs. Anticoagulants, such as danaparoid sodium (DA), inhibit various types of inflammation; however, the anti-inflammatory mechanism of action is not well understood. Given that heat stroke is a severe inflammatory response disease, we hypothesized that DA could inhibit inflammation from heat stress and prevent acute heat stroke. MATERIALS AND METHODS: Male Wistar rats were given a bolus injection of saline or DA (50 U/kg body weight) into the tail vein just prior to heat stress (42 °C for 30 min). Markers of inflammation were then determined in serum and tissue samples. RESULTS: In rats pretreated with DA, induction of cytokines (interleukin [IL]-1ß, IL-6, and tumor necrosis factor [TNF]-α), nitric oxide (NO), and high mobility group box 1 (HMGB1) protein were reduced compared with saline-treated rats. Histologic changes observed in lung, liver, and small intestine tissue samples of saline-treated rats were attenuated in DA-treated rats. Moreover, DA pretreatment improved survival in our rat model of heat stress-induced acute inflammation. CONCLUSION: Collectively, our findings demonstrate that DA pretreatment may have value as a new therapeutic tool for heat stroke.

Distribution and mitogen response of peripheral blood lymphocytes after exertional heat injury.

To determine whether immune disturbances during exertional heat injury (EHI) could be distinguished from those due to exercise (E), peripheral lymphocyte subset distributions and phytohemagglutinin-stimulated CD69 mitogen responses as discriminated by flow cytometry were studied in military recruits [18.7 +/- 0.3 (SE) yr old] training in warm weather. An E group (3 men and 3 women) ran 1.75-2 miles. During similar E, 11 recruits (10 men and 1 woman) presented with suspected EHI. EHI (40.4 +/- 0.3 degrees C) vs. E (38.6 +/- 0.2 degrees C) body temperature was significantly elevated (P < 0.05). Heat illness was largely classified as EHI, not heatstroke, because central nervous system manifestations were generally mild. Blood was collected at E completion or EHI onset (0 h) and 2 and 24 h later. At 0 h (EHI vs. E), suppressor, natural killer, and total lymphocyte counts were significantly elevated, helper and B lymphocyte counts remained similar, and the helper-to-suppressor ratio was significantly depressed. By 2 h, immune cell dynamics between groups were similar. From 0 to 24 h, T lymphocyte subsets revealed significantly reduced phytohemagglutinin responses (percent CD69 and mean CD69 fluorescent intensity) in EHI vs. E. Thus immune cell dynamics with EHI were distinguishable from E. Because heat stress as reported in exercise or heatstroke is associated with similar immune cell disturbances, these findings in EHI contributed to the suggestion that heat stress of varying severity shares a common pathophysiological process influencing the immune system.

Presence of antibody against the inducible Hsp71 in patients with acute heat-induced illness.

Antibodies against heat shock or stress proteins (Hsps) have been reported in a number of diseases in which they may be involved in the pathogenesis of the disease or may be of use for prognosis. Heat-induced diseases, such as heat cramps, heat exhaustion, or heat stroke, are frequent in hot working or living environments. There are still few investigations on the presence and possible significance of autoantibodies against Hsps in heat-induced illnesses. Using an immunoblotting technique with recombinant human Hsps, we analyzed the presence and titers of antibodies against Hsp60, Hsp71, and Hsp90alpha, and Hsp90beta in a group of 42 young male patients who presented with acute heat-induced illness during training. We also examined the presence of antibody against Hsp71 in a second group of 57 patients with acute heat-induced illness and measured the changes in titers of anti-Hsp71 antibodies in 9 patients hospitalized by emergency physicians. In the first group of young persons exercising in a hot environment, the occurrence of antibodies against Hsp71 and Hsp90alpha was significantly higher among individuals with symptoms of heat-induced illness (P < 0.05) than in the matched group of nonaffected exercising individuals. Moreover titers of antibody against Hsp71 were higher in individuals of the severe and mild heat-induced illness groups, the highest titer being found in the most severe cases. The results from the second group of 57 heat-affected patients exposed to extreme heat were similar. Again, patients with the more severe heat-induced symptoms showed a significantly higher incidence of antibodies to Hsp71 than controls and the titer of anti-Hsp71 was higher in the severely affected group. Finally, in a study of 9 patients, it was observed that the titer of anti-Hsp71 decreased during recovery from severe heat symptoms. These results suggest that measurement of antibodies to Hsps may be useful in assessing how individuals are responding to abnormal stress within their living and working environment and may be used as one biomarker to evaluate their susceptibility to heat-induced diseases.

Concentrations of soluble tumor necrosis factor and interleukin-6 receptors in heatstroke and heatstress.

OBJECTIVE: Increased proinflammatory cytokine concentrations have been implicated in the pathogenesis of heatstroke. Soluble cytokine receptors can modulate circulating cytokine activities. We examined the possible role of soluble tumor necrosis factor receptors (sTNFR 60, sTNFR 80) and interleukin-6 receptor (sIL-6R) in heatstroke by determining their concentrations before and after cooling, as well as in heatstressed controls. DESIGN: Prospective controlled study. SETTING: Heatstroke Center, Makkah, Saudi Arabia (1993 pilgrimage). PATIENTS: Twenty-five consecutive heatstroke patients before and after cooling, 14 heatstressed controls (HSC), and 13 normal controls (NC). MEASUREMENTS AND MAIN RESULTS: Concentrations of sTNFR 60, sTNFR 80, and sIL-6R, as well as their ligands, were measured using commercially available enzyme-linked immunosorbent assay kits. Mean sTNFR 60 concentration was increased in heatstroke (p <.0001, vs. NC; p < .0001, vs. HSC) and in HSC (p = .004, vs. NC). Mean sTNFR 80 concentration was increased in heatstroke and decreased in HSC (p = .01, heatstroke vs. HSC). Mean sIL-6R concentration was decreased in heatstroke and increased in HSC (p = .04, heatstroke vs. NC; p = .001, heatstroke vs. HSC). IL-6 was undetectable in NC and mean IL-6 concentration was more increased in heatstroke than in HSC (p = .001). Rectal temperature and creatinine concentrations correlated significantly with sTNFR 60, sTNFR 80, sIL-6R, and IL-6 concentrations. After cooling, mean concentrations of sIL-6R and sTNFR 80 increased significantly, whereas the mean sTNFR 60 concentration did not change. Residual neurologic deficits were associated with higher precooling IL-6 (p = .002) and postcooling sTNFRs (p < .0001) concentrations. CONCLUSIONS: Significant changes in cytokine receptor concentrations are associated with heatstress. In heatstroke, the changes are more pronounced, and for some cytokine receptors, the changes are in the opposite direction (compared with changes in heatstress). Concentrations of IL-6 and sTNFRs correlate with hyperthermia and outcome. Cooling did not normalize sTNFR concentrations, suggesting failure to control the inflammatory response.

The role of cytokines in heat stroke.

Heat stroke is a disease characterized by high fever. Cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-delta) play a major role in fever production. In the current studies, eight patients with heat stroke were enrolled in a cytokine studies. Serum cytokine levels of these patients were determined by EIA methods, and in vitro IL-1 and IL-1 inhibitor production were determined by murine thymocyte proliferation assay and/or EIA. Significantly high levels of circulating IL-1, TNF-delta, and IL-6 were demonstrated. Positive correlations were demonstrated between the body temperature and the level of IL-1 beta, and the cooling time and level of serum IL-1 beta. In addition, monocytes from heat stroke patients after complete recovery, secreted a much higher amount of IL-1 than did normal volunteers. However, there was no difference in IL-1 inhibitor production. These results indicate that cytokines may play a major role in the pathogenesis of heat stroke, and the ability to make different amounts of IL-1 in response to exogenous stimulation appear to be risk factors for an attack of heat stroke.

[The effect of a high external temperature on cellular immunity]. / Vliianie vysokoi vneshnei temperatury na sostoianie kletochnogo immuniteta.

The study was made of spleen cells proliferative response to mitogens PHA, Con A or alloantigens in relation to hyperthermia effects. Acute hyperthermia (rectal temperature 42 degrees) enhanced lymphocyte function, proliferative responses to allo-antigens, PHA and Con A increased. Thermal shock was associated with suppression of the spleen cell response. Mice suffering from hyperthermia for 20 min (43-44 degrees) daily during 10, 20 and 30 days showed suppressed T-cell immune response. Normal splenocyte proliferation recovered 40 days after hyperthermia induction.