Allergoid-specific T-cell reaction as a measure of the immunological response to specific immunotherapy (SIT) with a Th1-adjuvanted allergy vaccine.

BACKGROUND: Specific immunotherapy (SIT) is believed to modulate CD4+ T-helper cells. In order to improve safety, SIT vaccines are often formulated with allergoids (chemically modified allergens). Interaction between T-cells and allergoids is necessary to influence cellular cytokine expression. There have been few reports on identification the early cellular effects of SIT. METHOD: Patients allergic to grass and/or mugwort pollen (n= 21) were treated with a 4-shot allergy vaccine (Pollinex Quattro) containing appropriate allergoids (grass/rye and/or mugwort) adsorbed to L-tyrosine plus a Th1 adjuvant, monophosphoryl lipid A (MPL). Fourteen grass-allergic patients served as untreated controls. Using the peripheral blood mononuclear cells of these patients, an optimized lymphocyte transformation test (LTT) was employed to monitor the in vitro proliferative response of T-cells to an allergoid challenge (solubilised Pollinex Quattro) before the first and last injection and then 2 and 20 weeks after the final injection. Control challenges utilised preparations of a similar pollen vaccine without the adjuvant MPL and a tree pollen vaccine with and without MPL. RESULTS: The LTT showed increased LTT stimulation indices (SI) in 17/20 SIT patients when the solublised vaccine preparation was used as a challenge before the last injection and 2 weeks after, in comparison to pre-treatment levels. Twenty weeks after therapy, the SI decreased to baseline level. A vaccine challenge without MPL gave lower SI levels. A challenge of a clinically inappropriate tree allergoid vaccine gave no response, and a nontreated group also showed no response. CONCLUSION: Following a short-course SIT adjuvated with MPL, challenges of allergoids were shown to activate allergen-specific T cells in vitro. There was an additional stimulating effect when the challenge was in combination with MPL. There were no non-specific effects of MPL, shown by the tree allergoid/MPL control. The timing of the response was closely correlated to the treatment course; reactivity fell two weeks after the final injection and 20 weeks later it was at baseline level. Thus an immunological response to SIT was detected after very few injections. This methodology could provide a basis for monitoring the immediate progress of allergy vaccinations.

Effects of a multiple mild infra-red-A induced hyperthermia on central and peripheral pulse waves in hypertensive patients.

The paper reports on the effects of multiple whole-body infra-red-A irradiational (IRA) on 13 male patients known to have stage I or stage II essential arterial hypertension (WHO definition). The peripheral blood pressure was decreased significantly by IRA exposures. The lowered diastolic blood pressure lasted into posttreatment time. This effect is regarded as a consequence of an improvement in peripheral haemodynamics. A measure of this improvement is the different shape of the blood pressure pulse waves. Calculation and comparison of the spectral components of the recorded pulse signals show that these components are useful for a prediction of the blood pressure lowering effect.

[Characterization of the effect of retransfusion of UV-irradiated autologous blood--synoptic examination of clinical, metabolic, rheologic and hemodynamic results in patients with arterial occlusive disease]. / Charakterisierung des Effektes der Retransfusion uv-bestrahlten Eigenblutes (UVB)-synoptische Betrachtung klinischer, metabolischer, rheologischer und hämodynamischer Ergebnisse an Patienten mit arterieller Verschlusskrankheit.

In 6 inpatients with angiographically ascertained arterial obstructive disease the influence of the retransfusion of uv-radiated own blood on metabolic, haemorheological, clinical and haemodynamic parameters was examined. In 4 patients a pseudoradiation was performed as control. The results confirm that under the ultra-violet radiation changes develop in the sense of a normalisation of the parameters examined. Here an improved walking capacity is accompanied by an improvement of the O2- and substrate utilisation of the tissue and the flowing properties. On the basis of the results the improvement of the microcirculation under ultra-violet radiation is to be derived. The sites of action of the ultra-violet radiation are shown in the causal chain in arterial obstructive diseases and partial steps of the mode of action are described.

[Studies in experimental animal models of the effect of ultraviolet radiation (UVC) on blood and isolated cell populations]. / Tierexperimentelle Modelluntersuchungen zur Wirkung von ultravioletter Strahlung (UVC) auf Blut und isolierte Zellpopulationen.

The cellular and molecular basis of the therapeutically used effect of reinjected ultraviolet ( UVC ) irradiated blood is unknown. First approaches to that problem were made in this study by aid of model experiments. Neither the spontaneous degranulation nor the antigen-induced histamine release from rat connective tissue mast cells (in vivo) was influenced by the injection (i.v.) of ultraviolet irradiated blood or blood lymphocytes. By comparison of the effect of ultraviolet light on blood lymphocytes (number of dead cells, strength of chemoluminescence) after irradiation of the isolated cells and the unfractionated blood respectively, we could show that the strong light absorption within the blood sample prevents damage or functional alterations of the blood lymphocytes. The compound 48/80-induced histamine release from rat peritoneal mast cells can be completely inhibited by ultraviolet irradiation (0.6 mJ/cm2) without increasing the spontaneous histamine release.

[Systemic effects of ultraviolet, visible and infrared radiation in serial whole body irradiation. II. Effect on the immune cells of the skin]. / Systemische Effekte der Ultraviolett-, sichtbaren bzw. Infrarot-Strahlung bei seriellen Ganzkörperbestrahlungen. II. Der Einfluss auf die Immunzellen der Haut.

Before and after skin treatment by ultraviolet radiation, infrared radiation or visible light the ability of polymorphonuclear leukocytes (PMN) to form oxygen intermediates was investigated in 31 healthy volunteers. Superoxide production was evaluated photometrically as the reduction of Iodonitrotetrazoliumchloride (INT). After whole body treatment by 4 UV exposures all persons exhibited significantly enhanced rates of INT-reduction for 26-62 days. The in vivo half-time of PMN is 5-7 hours. Therefore a direct effect of irradiation over that long period is rather unlikely, suggesting that mediators should play a crucial role in signal transduction from the skin to the peripheral blood cells. Most likely candidates for connective links are interferon-gamma (IFN-gamma), granulocyte-monocyte colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF).

[Therapeutic use of ultraviolet irradiation in medicine--scientific principles and clinical results]. / Die therapeutische Nutzung der Ultraviolettstrahlung in der Medizin--wissenschaftliche Grundlagen und klinische Ergebnisse.

Sunshine is one of mankind's oldest remedies. Merely forgotten, UV light treatment came back recently due to (1) technological progress, providing particular UV wavelengths (2) basic research, discovering mode of action at molecular level, and (3) rising knowledge about skin as the primary target. Human skin is a rather difficult organ, possessing a considerable part of the immune system, the so-called skin associated lymphoid tissue. Different biological effects are caused by UV irradiation at different wavelengths. UV radiation alone as well as together with a photosensitizer also can cause systemic effects. Dealing with these, results of basic research and their application on modern treatment of some skin diseases, transplantation medicine, non-specific resistance system, and treatment of cardiovascular diseases are discussed.

[Hemodynamics of patients with essential hypertension in mild infrared hyperthermia]. / Untersuchungen zur Hämodynamik bei Patienten mit essentieller Hypertonic unter milder Infrarot-Hyperthermie (IRA-Therm II).

Hyperthermia therapy in hypertensive patients is been discussed as an effective treatment. The aim of this study was to control the behaviour of circulation in conditions of hyperthermia. A group of 6 males, 32-53 years old, suffering from essential hypertension stage I-II underwent a single whole body-irradiation with near infrared (IRA), lasting over one hour. The body temperature rises up to maximal 38.5 degrees C. Before, during and after treatment the blood pressure (BP), the heart rate (HR), the stroke volume (SV), the cardiac output (CO) and the ejection fraction - measured by radionuclide ventriculography - where estimated and the peripheral arterial mean pressure (Pm), the ejection resistance (AW) and the Total peripheral resistance (TpW) were calculated. During irradiations there was a significant decrease of BP, AW and TpW. HR, SV, CO and EF increased significantly. Due to IRA irradiations there was a change in microcirculation with the consequence of lowering the blood pressure. The concomitant stimulation of the heart was well compensated as shown by CO, SV and EF.

[Serial infrared and ultraviolet whole body irradiation and placebo and ultraviolet irradiation of autologous venous blood in peripheral arterial occlusive disease. 1. Treadmill ergometry, metabolic, rheologic and hemodynamic parameters]. / Serielle Infrarot- und UV-Ganzkörperbestrahlung sowie Schein- und UV-Bestrahlung venösen Eigenblutes bei peripherer arterieller Verschlusskrankheit. 1. Laufbandergometrie, metabolische, rheologische und hämodynamische Parameter.

In 21 patients suffering from obstructive peripheral arterial disease stage II according to Fontaine, therapeutic efficacy of serial whole body irradiations (infrared or ultraviolet radiation) and pretended or real ultraviolet light blood irradiations was evaluated. Before, during and after treatment the following parameters were monitored: walking distance, oxygen partial pressure (quasi-arterial/venous), flow properties of blood (appearant blood viscosity, hemodynamics (peak flow, ultrasonics). There were no significant changes following both modalities of whole body irradiations either by sunshine-like ultraviolet light nor by infrared radiation, nor by pretended blood irradiation. In the same patients mean walking distance was prolonged threefold after ultraviolet irradiation of the patient's own venous blood and subsequent retransfusion. Simultaneously, oxygen utilisation was improved (enlarged arterial/venous difference), lactate concentration was decreased and apparent blood viscosity was diminished, whereas blood flow remained unchanged or only slightly improved. In this way the circulus vitiosus of obstructive peripheral arterial disease can be overcome. As a consequence of blood irradiation walking distance enlarges, providing better chances for physical training, which helps to extend walking distance furthermore.

[Experimental studies on the rheologic behavior of blood in ultraviolet therapy]. / Experimentelle Untersuchungen zum rheologischen Verhalten von Blut bei Ultraviolettbestrahlung (UVB).

The increased apparent blood viscosity proved in peripheral circulatory disease, the frequent failure of therapy by means of vasodilating medicaments and the successful therapy with the help of ultraviolet radiation of blood (UVB) by means of various techniques motivated investigations of the flow properties of blood with UVB. In six patients with angiologically ascertained arterial occlusive disease the flow properties of blood were investigated under standardized conditions by both viscosimetric techniques and independent of it by means of the centrifugation method. Plasma viscosity, apparent blood viscosity, parameters of aggregation and deformation of erythrocytes were determined before and after fictitious UVB on the hand one and before and after real UVB on the other hand. It was shown that within the limit of measurement accuracy there were no significant differences between fictitious and real UVB in plasma viscosities. Both the aggregation parameter of the centrifugation method and the apparent blood viscosity for low shear gradients before the 3rd UVB and all following ones differed significantly from those of the first UVB. No changes were found in the deformation parameters HCC infinity and the apparent viscosity for high shear gradients during UVB therapy. Possible mechanisms leading to the demonstrated improvements of the flow properties of blood by means of UVB are discussed.

[Systemic effects of ultraviolet, visible and infrared radiation in serial whole body irradiation. I. Oxygen utilization, flow properties of blood, hemodynamics, blood components and phagocytosis]. / Systemische Effekte der Ultraviolett-, sichtbaren bzw. Infrarotstrahlung bei seriellen Ganzkörperbestrahlungen. I. Sauerstoffutilisation, Fliesseigenschaften des Blutes, Hämodynamik, Blutbestandteile und Phagozytose.

31 healthy volunteers at the age of 19 to 29 years underwent whole-body irradiations by either ultraviolet radiation (NARVA UVS 65-2; continuous sunshine-like emission, predominantly UVA plus 8% UVB; cumulative doses after 4 and 20 irradiations 8.8 J/cm2 and 51.0 J/cm2, respectively), or visible light (emission of a 3,500 Watt lamp HGMI 3500 DL, Tungsram CSSR, filtered through 6 mm window glass; cumulative dose 267.0 J/cm2 after 4 irradiations) or infrared radiation (250 Watt infrared lamps NARVA "Biotherm", emitting more than 70% infrared radiation; cumulative dose 159.0 J/cm2 after 4 irradiations). Before, during and after the irradiation series the following investigations were made: Arterial and venous oxygen pressure, oxygen utilization index; flow properties of peripheral blood (plasma viscosity, erythrocyte aggregation kinetics, apparent blood viscosity); hemodynamics (veineal plethysmography, 133Xenon clearance, functional diameter of small blood vessels, peripheral blood pressure), phagocytotic capacity of polymorphonuclear white blood cells; hematological parameters (blood sedimentation rate, polymorphonuclear and eosinophilic blood cells, red blood cells, hemoglobin, hematocrit), serum proteins (IgG, IgA, IgM, complement C3, alpha-1-glycoprotein, alpha-1-antitrypsin, haptoglobin, transferrin); calcium and phosphate in serum. As far as irradiance, dose and treatment frequencies are concerned, the experimental conditions were very similar to those in phototherapeutical practice. Under these circumstances there were no hints for unwanted early effects after application of all the three kinds of optical radiation used in that study. Considerable systemic responses exclusively were found by use of ultraviolet radiation. Under these experimental conditions according to dermatological phototherapy it has been proven the following biopositive systemic responses are due to happen: increase of serum calcium and phosphate, improvement of blood oxygen utilization, improvement of blood flow properties, and enhanced phagocytic capacity of polymorphonuclear white blood cells. Regarding the parameters taken in that study, no early unwanted side effects are to expect after therapeutical application of rather large doses of visible light or infrared radiation.

[Effect of a single mild infrared A hyperthermia on body temperature, heart rate, blood pressure and blood viscosity in healthy probands and patients with stage I and II arterial hypertension]. / Wirkung einer einmaligen milden Infrarot-A-Hyperthermie auf Körpertemperatur, Herzfrequenz, Blutdruck und Blutviskosität bei Gesunden und Patienten mit arterieller Hypertonie der Stadien I und II.

Report on mild and single whole body-irradiations with near infrared (IRA). The central body temperature went up to 38.5 degrees C in 9 healthy subjects and 9 patients known as having essential arterial hypertension of the stages I or II. In case of hypertensive patients a single exposure decreased significantly both arterial and venous blood pressure as well as the resulting mean arterial blood pressure. This beneficial effect lasted for at least 24 hours. Besides that, improvement of peripheral hemodynamics and plasma viscosity also was proven. Obviously, improved peripheral hemodynamics is linked to that blood pressure lowering effect which happens due to dilatation of peripheral blood vessels.