Sun exposure induces rapid immunological changes in skin and peripheral blood in patients with psoriasis.

BACKGROUND: Ultraviolet (UV) radiation has immunosuppressive effects and heliotherapy is a well-described treatment modality for psoriasis. OBJECTIVES: To characterize early sun-induced immunological changes both local and systemic in patients with psoriasis. METHODS: Twenty patients with moderate to severe psoriasis were subjected to controlled sun exposure on Gran Canaria, Canary Islands, Spain. Psoriasis Area and Severity Index (PASI) scores were evaluated. Skin biopsies were obtained from lesional and nonlesional skin in 10 patients at baseline and on day 16 and from five additional patients on day 2. Specimens were examined with immunohistochemistry and polymerase chain reaction. Blood samples were obtained from all patients at the same time points and were examined for T-cell subsets and cytokine production. RESULTS: Significant clinical improvement was achieved during the study period. CD4+ and CD8+ T cells in lesional skin were significantly reduced in both the epidermis and dermis. In contrast, dermal FOXP3+ T cells were relatively increased. In the peripheral blood skin homing cutaneous lymphocyte-associated antigen (CLA)+ T cells were significantly decreased after only 1 day in the sun and in vitro stimulated peripheral blood mononuclear cells demonstrated reduced capacity to secrete cytokines after 16 days. CONCLUSIONS: Our data show that clinical improvement of psoriasis following sun exposure is preceded by a rapid reduction in local and systemic inflammatory markers, strongly suggesting that immune modulation mediated the observed clinical effect. We cannot completely rule out that other mechanisms, such as stress reduction, may contribute, but it is extensively documented that UV irradiation is a potent inducer of immunosuppression and we therefore conclude that the observed effect was primarily due to sun exposure.

Complement activation and increased systemic and pulmonary vascular resistance indices during infusion of postoperatively drained untreated blood.

In nine healthy young patients, operated on for thoracic scoliosis, a pulmonary artery catheter was inserted for the study of haemodynamic variables and blood sampling during autologous transfusion of postoperatively drained blood. At 1-3 h after wound closure, 10 ml kg/body weight of drained untreated blood from the wound was collected and recirculated over a l-h period. The concentration of the complement activation product, C3bc, increased from a mean of 5.4 (SD 1.5) AU ml-1 before infusion to 11.1 (3.9) AU ml-1 during infusion and then returned to 7.8 (2.8) AU ml-1 after infusion. The concentration of the terminal complement complex (TCC) increased from 0.5 (0.2) to 1.3 (0.5) AU ml-1 and was reduced to 0.7 (0.3) AU ml-1 after infusion. Only TCC exceeded the reference values which are 14 AU ml-1 for C3bc and 1.0 AU ml-1 for TCC. Pulmonary vascular resistance index concomitantly increased from a mean of 130 (SD 52) to 195 (88) dyn s cm-5 m-2 and was reduced to 170 (86) dyn s cm-5 m-2 after infusion. Systemic vascular resistance index increased from a mean of 1238 (SD 403) to 1349 (473) dyn s cm-5 m-2 and returned to 1196 (401) dyn s cm-5 m-2 after infusion. White blood cell count (WCC) increased from 14.4 (4.3) x 10(9) litre-1 before infusion to 17.8 (7.2) x 10(9) litre-1 during and after infusion. No change in platelet count during infusion was observed. There were no differences in WCC or platelet count between mixed venous or peripheral arterial blood. Pulmonary and systemic vascular resistance indices may be influenced by activated complement in drained untreated blood when it is recirculated.

Removal of activated complement from shed blood: comparison of high- and low-dilutional haemofiltration.

BACKGROUND: Perioperative blood salvage is associated with release of inflammatory mediators. Depending on type of processing, the complement system is activated to some extent in the final blood product. The aim of the present study was to evaluate a haemofiltration technique concerning complement system activation and whether the volume of added saline will have an influence on the elimination of activated complement during processing. METHODS: Sixteen patients undergoing total hip arthroplasty received wound blood salvaged intraoperatively with a haemofiltration technique. Saline was added to the reservoir for washing in a ratio of 1:1 or 5:1 of estimated blood volume. Samples for determination of the anaphylatoxins C3a and C5a, and the terminal SC5b-9 complement complex (TCC) were drawn from the patients, the collected blood, the ultrafiltrate and the processed blood. RESULTS: Increased concentrations of C3a, C5a and TCC were found in aspirated and processed blood. Haemofiltration did not reduce the concentrations of these factors, except that of C3a in the group where saline was added in a ratio of 5:1. There were no increased concentrations of C3a, C5a or TCC in the patient plasma after reinfusion. No differences in blood pressure, heart rate, pH, arterial oxygen tension, arterial carbon dioxide tension, or base excess were found in association with reinfusion of the blood. CONCLUSION: Collected shed blood washed through haemofiltration contained moderately elevated concentrations of C3a, C5a and TCC. Reinfusion of the blood neither led to increased systemic concentrations of complement activation products, nor to disturbances in haemodynamic or biochemical parameters.

Adhesion molecule expression and complement activation in vessel walls in synovial tissue from patients with chronic inflammatory joint disease.

Histopathology demonstrating a manifest vasculitis is a rare event in synovial tissue (ST) from patients with chronic inflammatory joint disease. As a possibly more subtle sign of a vasculitic process, complement activation in vessels in ST was studied. In the same tissues, the expression of the adhesion molecules ICAM-1 and E-selectin in vessel walls was examined, to see if the expression was related to vasculitic processes. The study was performed by use of direct immunofluorescence technique on cryostat sections of ST, using mouse monoclonal antibodies to the terminal complement complex (TCC, C5b-9), ICAM-1 and E-selectin. Expression of ICAM-1 was found in the vessel walls in all of 28 tissues tested, whereas E-selectin was found in 4 cases and TCC in 11. E-selectin and TCC were found together in only 1 tissue. The study supports the view that ICAM-1 is always, or nearly always, present in vessel walls in synovial tissue from patients with chronic inflammatory joint disease. E-selectin and TCC may also be present, but the lack of association between these two proteins suggests that the mechanism leading to a complement mediated vasculitic process is different from that causing expression of E-selectin.

Release of interleukin 6 and activation of complement during and after paediatric cardiopulmonary bypass. Effect of autotransfusion of shed mediastinal blood and ultrafiltration.

Interleukin-6 (IL-6) and the complement activation products C3bc and terminal complement complex (TCC) were measured in three groups of children undergoing open heart surgery. One group was treated with intraoperative extracorporeal ultrafiltration and postoperative autotransfusion of shed mediastinal blood, one group was subjected to autotransfusion only and in one group none of these procedures were performed. No differences between the groups were observed concerning the degree of complement activation. Peak and total accumulated level of IL-6 was significantly higher in the group subjected to ultrafiltration and autotransfusion compared to the group treated conventionally with no interventions. IL-6 may be a sensitive marker of maneuvres increasing the inflammatory load during and after open heart surgery in children.

[Reduced blood utilization in hip arthroplasty. Introduction of a blood preservation program]. / Reduksjon i blodforbruket ved hofteprotesekirurgi. Gjennomføring av et blodspareprogram.

In spring 1992 a blood conservation programme was established at Nordland Central Hospital with emphasis on indications for blood transfusion and intraoperative blood salvage (cell-saver). Medical records from all patients who underwent hip arthroplasty during the period 1 June 1991 to 28 February 1994 were examined. Mean transfusion of homologous SAGMAN-blood (bank blood) was substantially reduced during the period: for total prosthesis (n = 192) from 2.6 to 1.1 units per operation (p < 0.0001) and for hemiprosthesis (n = 66) from 3.1 to 0.9 units per operation (p = 0.0202). The percentage of patients in each of these two groups who did not receive blood transfusion at all increased from 18 to 61 in the first group (p < 0.0001) and from 24 to 65 (p = 0.0202) in the second. The substantial reduction of bank blood transfusion in this material conforms with current international transfusion guidelines. A particular benefit, considering the risk of transfusing contagious blood, is the marked increase in the number of patients who did not receive any blood product at all.