Optimal sunscreen use, during a sun holiday with a very high ultraviolet index, allows vitamin D synthesis without sunburn.

BACKGROUND: Sunlight contains ultraviolet (UV)A and UVB radiation. UVB is essential for vitamin D synthesis but is the main cause of sunburn and skin cancer. Sunscreen use is advocated to reduce the sun's adverse effects but may compromise vitamin D status. OBJECTIVES: To assess the ability of two intervention sunscreens to inhibit vitamin D synthesis during a week-long sun holiday. METHODS: The impact of sunscreens on vitamin D status was studied during a 1-week sun holiday in Tenerife (28° N). Comparisons were made between two formulations, each with a sun protection factor (SPF) of 15. The UVA-protection factor (PF) was low in one case and high in the other. Healthy Polish volunteers (n = 20 per group) were given the sunscreens and advised on the correct application. Comparisons were also made with discretionary sunscreen use (n = 22) and nonholiday groups (51·8° N, n = 17). Sunscreen use in the intervention groups was measured. Behaviour, UV radiation exposure, clothing cover and sunburn were monitored. Serum 25-hydroxyvitamin D3 [25(OH)D3 ] was assessed by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Use of intervention sunscreens was the same (P = 0·60), and both equally inhibited sunburn, which was present in the discretionary use group. There was an increase (P < 0·001) in mean ± SD 25(OH)D3 (28·0 ± 16·5 nmol L-1 ) in the discretionary use group. The high and low UVA-PF sunscreen groups showed statistically significant increases (P < 0·001) of 19·0 ± 14·2 and 13·0 ± 11·4 nmol L-1 25(OH)D3 , respectively with P = 0·022 for difference between the intervention sunscreens. The nonholiday group showed a fall (P = 0·08) of 2·5 ± 5·6 nmol L-1 25(OH)D3 . CONCLUSIONS: Sunscreens may be used to prevent sunburn yet allow vitamin D synthesis. A high UVA-PF sunscreen enables significantly higher vitamin D synthesis than a low UVA-PF sunscreen because the former, by default, transmits more UVB than the latter. What's already known about this topic? Action spectra (wavelength dependence) for erythema and the cutaneous formation of vitamin D overlap considerably in the ultraviolet (UV)B region. Theoretically, sunscreens that inhibit erythema should also inhibit vitamin D synthesis. To date, studies on the inhibitory effects of sunscreens on vitamin D synthesis have given conflicting results, possibly, in part, because people typically apply sunscreen suboptimally. Many studies have design flaws. What does this study add? Sunscreens (sun protection factor, SPF 15) applied at sufficient thickness to inhibit sunburn during a week-long holiday with a very high UV index still allow a highly significant improvement of serum 25-hydroxyvitamin D3 concentration. An SPF 15 formulation with high UVA protection enables better vitamin D synthesis than a low UVA protection product. The former allows more UVB transmission.

Sunscreen applied at ≥ 2 mg cm-2 during a sunny holiday prevents erythema, a biomarker of ultraviolet radiation-induced DNA damage and suppression of acquired immunity.

BACKGROUND: Sun protection factor (SPF) is assessed with sunscreen applied at 2 mg cm-2 . People typically apply around 0·8 mg cm-2 and use sunscreen daily for holidays. Such use results in erythema, which is a risk factor for skin cancer. OBJECTIVES: To determine (i) whether typical sunscreen use resulted in erythema, epidermal DNA damage and photoimmunosuppression during a sunny holiday, (ii) whether optimal sunscreen use inhibited erythema and (iii) whether erythema is a biomarker for photoimmunosuppression in a laboratory study. METHODS: Holidaymakers (n = 22) spent a week in Tenerife (very high ultraviolet index) using their own sunscreens without instruction (typical sunscreen use). Others (n = 40) were given SPF 15 sunscreens with instructions on how to achieve the labelled SPF (sunscreen intervention). Personal ultraviolet radiation (UVR) exposure was monitored electronically as the standard erythemal dose (SED) and erythema was quantified. Epidermal cyclobutane pyrimidine dimers (CPDs) were determined by immunostaining, and immunosuppression was assessed by contact hypersensitivity (CHS) response. RESULTS: There was no difference between personal UVR exposure in the typical sunscreen use and sunscreen intervention groups (P = 0·08). The former had daily erythema on five UVR-exposed body sites, increased CPDs (P < 0·001) and complete CHS suppression (20 of 22). In comparison, erythema was virtually absent (P < 0·001) when sunscreens were used at ≥ 2 mg cm-2 . A laboratory study showed that 3 SED from three very different spectra suppressed CHS by around ~50%. CONCLUSIONS: Optimal sunscreen use prevents erythema during a sunny holiday. Erythema predicts suppression of CHS (implying a shared action spectrum). Given that erythema and CPDs share action spectra, the data strongly suggest that optimal sunscreen use will also reduce CPD formation and UVR-induced immunosuppression.

Children sustain high levels of skin DNA photodamage, with a modest increase of serum 25-hydroxyvitamin D3 , after a summer holiday in Northern Europe.

BACKGROUND: Childhood solar ultraviolet radiation (UVR) exposure increases the risk of skin cancer in adulthood, which is associated with mutations caused by UVR-induced cyclobutane pyrimidine dimers (CPD). Solar UVR is also the main source of vitamin D, essential for healthy bone development in children. OBJECTIVES: To assess the impact of a 12-day Baltic Sea (54° N) beach holiday on serum 25-hydroxyvitamin D3 [25(OH)D3 ] and CPD in 32 healthy Polish children (skin types I-IV). METHODS: Blood and urine were collected before and after the holiday and assessed for 25(OH)D3 and excreted CPD, respectively, and personal UVR exposure was measured. Diaries were used to record sunbathing, sunburn and sunscreen use. Before- and after-holiday skin redness and pigmentation were measured by reflectance spectroscopy. RESULTS: The average ± SD daily exposure UVR dose was 2·4 ± 1·5 standard erythema doses (SEDs), which is borderline erythemal. The mean concentration of 25(OH)D3 increased (× 1·24 ± 0·19) from 64·7 ± 13·3 to 79·3 ± 18·7 nmol L-1 (P < 0·001). Mean CPD increased 12·6 ± 10·0-fold from 26·9 ± 17·9 to 248·9 ± 113·4 fmol µmol-1 creatinine (P < 0·001). Increased 25(OH)D3 was accompanied by a very much greater increase in DNA damage associated with carcinogenic potential. Overall, skin type had no significant effects on behavioural, clinical or analytical outcomes, but skin types I/II had more CPD (unadjusted P = 0·0496) than skin types III/IV at the end of the holiday. CONCLUSIONS: Careful consideration must be given to the health outcomes of childhood solar exposure, and a much better understanding of the risk-benefit relationships of such exposure is required. Rigorous photoprotection is necessary for children, even in Northern Europe.

Personal UVR exposure of farming families in four European countries.

BACKGROUND: The main risk factor for skin cancer is ultraviolet radiation (UVR). Farming families living in rural areas with easy outdoor access may experience excessive UVR exposure. Differences between countries in latitude, altitude and sun behaviour could result in different personal UVR exposures. However, no studies have examined this until now. OBJECTIVES: To determine personal UVR exposure in work and leisure situations among farming families in Europe. METHODS: Prospective cohort study of farmers, their partners (spouses) and children in Denmark (DK), Poland (PL), Austria (AT), and Spain (ES) from 2009 to 2011. Personal UVR exposure and sun behaviour were recorded by dosimetry and diaries. RESULTS: Farmers' average daily UVR exposure on working days ranged from 1.4 SED (DK, AT) to 2.7 SED (ES). Corresponding figures for partners were: 0.6 SED (DK) to 1.9 SED (PL), and for children (day-care/school days): 0.7 SED (ES) to 1.3 SED (PL). DISCUSSION AND CONCLUSIONS: Farmers' UVR exposure was comparable to that of outdoor workers in previous studies and exceeded the recommended UVR exposure limits on 36% (DK, AT), 29% (PL) and 56% (ES) of their working days. Attention to sun protection for outdoor workers across Europe in preventing UVR-induced skin cancer is still needed.

Inflammatory response in patients undergoing colorectal cancer surgery: the effect of two different anesthetic techniques.

BACKGROUND: Anesthesia during surgery often induces an inflammatory response. The aim of this study was to establish and compare differences in inflammatory response among colorectal cancer surgery patients receiving either total intravenous anesthesia (TIVA) with propofol and remifentanil or inhalational anesthesia (INHAL) with sevoflurane and fentanyl. METHODS: After randomization, we included fifty consecutive patients undergoing colorectal cancer surgery in our study. TIVA patients received total intravenous anesthesia with propofol and remifentanil, while INHAL patients received inhalation anesthesia with sevoflurane in O2/air and fentanyl. Plasma concentrations of IL-8, IL-17, MPO, ICAM-1, V-CAM and L-selectin were quantified. Blood loss, body temperature and blood glucose levels were measured in patients both before and after surgery. RESULTS: In both groups, levels of IL-8, MPO, ICAM-1 and L-selectin decreased 60 min after the start of surgery (P<0.05, P<0.01, respectively) and 30 min post-surgery (P<0.05 for both groups). In the INHAL group, V-CAM levels were significantly lower 60 min after the start of surgery (P<0.01) and 30 min post-surgery (P<0.05). At 24 h post-surgery, V-CAM levels were significantly higher in both groups (P<0.01), while IL-17 levels significantly increased only in the INHAL group (P<0.05). Higher blood glucose levels were also observed in the INHAL group compared to that in the TIVA group (P<0.01). CONCLUSION: TIVA with propofol and remifentanil and INHAL with sevoflurane and fentanyl induced similar inflammatory responses during colorectal cancer surgery. We found that IL-17 cytokine levels were higher in patients anesthetized with sevoflurane and fentanyl.

Suberythemal ultraviolet B radiation alters the expression of cell cycle-related proteins in the epidermis of human subjects without leading to photoprotection.

BACKGROUND: Deregulation of the cell cycle proteins is one of the critical factors leading to cutaneous carcinogenesis. OBJECTIVES: To monitor the expression of cell cycle proteins in the epidermis of subjects after repeated exposure to ultraviolet (UV) B radiation, and to test for the development of photoprotection by subsequent irradiation with a single erythemal UVB dose. METHODS: A total of 26 healthy volunteers were divided into four groups: group 1 (n = 9) were given whole-body UVB irradiation for 10 consecutive days with 0.7 minimal erythema dose (MED), group 2 (n = 9) were irradiated as in group 1 followed 24 h later by a single UVB dose of 3 MED on buttock skin, group 3 (n = 4) were irradiated with a UVB dose of 3 MED on buttock skin, and group 4 (n = 4) were not irradiated. Skin biopsies were collected 24 h after the final irradiation and stained for cyclins A, B1, D1, and p16, p18, p21, p27, p53, pRB, Bax and Bcl-2. RESULTS: The expression of cyclin D1, p18 and p21 was significantly higher in groups 1 and 2 compared with the nonirradiated group 4 controls and, in group 2, the expression of pRB, p53 and Bax was also increased. In group 3, only p53 and Bax proteins were significantly elevated compared with group 4. The expression of cyclin D1, p16, p18, p27, pRB and Bcl-2 was higher in group 2 compared with group 3. CONCLUSIONS: Suberythemal UVB radiation was sufficient to cause changes in the expression of several epidermal cell cycle proteins. When tested by irradiation with a single erythemal UVB dose following the repeated exposures, no photoprotection against the UV-induced alteration in cell cycle protein expression was apparent.

Complement split products and proinflammatory cytokines in intraoperatively salvaged unwashed blood during hip replacement: comparison between heparin-coated and non-heparin-coated autotransfusion systems.

BACKGROUND AND OBJECTIVES: The aim of the present study was to investigate the quality of shed blood collected in a new intraoperative autotransfusion system (Sangvia, AstraTech, Sweden) and to study whether heparin-coated surfaces in the device reduce the production of inflammatory mediators. MATERIAL AND METHODS: The study was randomized and prospective. Twelve total hip arthroplasty patients whose blood was collected with a device having a heparin-coated surface and 12 patients whose blood was collected with a device having a non-heparin-coated surface were included. Venous blood was drawn from the patients preoperatively. Intraoperatively 200 ml salvaged blood was collected and samples were also withdrawn; samples were obtained from the blood bag. RESULTS: Compared to venous blood, elevated concentrations of interleukin 6 (IL-6), IL-8, C3a and polymorphonuclear elastase were found in collected blood. No significant differences in inflammatory mediators were found between the heparin-coated and the non-heparin-coated groups. The median haemoglobin concentration in the salvaged blood was 74 g/l in both groups. Plasma haemoglobin and potassium concentrations were also elevated. There were no significant differences between the groups. CONCLUSION: The present study indicates that the blood salvaged intraoperatively contains elevated levels of complement split product and proinflammatory cytokines and that heparin-coated surfaces of the salvage device do not significantly influence the formation of inflammatory mediators.

Plasma concentration of procalcitonin and systemic inflammatory response syndrome after colorectal surgery.

BACKGROUND: To study whether plasma concentrations of procalcitonin (PCT), interleukin-6 (IL-6), complement 3a (C3a), C-reactive protein and white blood cell count (WBC) correlate with the presence of systemic inflammatory response syndrome (SIRS) during the early post-operative period after major colorectal surgery. METHODS: Prospective, observational study during the first 24 h post-operatively. The setting for the study was the operating theatre and the recovery unit at the university hospital. Fifty consecutive patients, operated on electively with major resection of the large bowel or rectum. PCT levels increased significantly to the maximum level 18 h postoperatively. PCT levels were significantly higher in the SIRS group in comparison to the non-SIRS group of patients 6 and 12 h after surgery (P < 0.05). The IL-6 levels were increased directly after the surgery and then decreased gradually in both study groups. Twenty-four hours after the surgery, C3a levels decreased and then returned to normal levels. Twenty-four hours post-operatively, patients with SIRS had a higher plasma concentration of C3a compared with patients without SIRS (P < 0.05). CRP and WBC increased during the study period in both groups (P < 0.05). CONCLUSIONS: During the early post-operative period after uncomplicated major abdominal surgery, SIRS was reflected by the increase in plasma PCT and C3a concentrations. IL-6, CRP and WBC increased to the same extend in both the SIRS and the non-SIRS group of patients.

Complement activation in prestorage leucocyte-filtered plasma.

Complement activation and generation of pro-inflammatory cytokines occur during storage of blood components. Prestorage leucocyte filtration of platelet concentrates and red cells diminishes the accumulation of leucocyte-derived cytokines during storage, however, transfusion reactions are not eliminated. We investigated inflammatory mediator release during storage of plasma and whole blood and the effect of prestorage leucocyte filtration of plasma. Twenty-four blood units were collected from healthy blood donors and stored for 35 days. Eight units were stored as whole blood, eight units as plasma and eight units as prestorage filtered plasma. Samples were collected weekly for analyses of potassium, leucocytes, free plasma haemoglobin, complement activation (C3a and SC5b-9) and pro-inflammatory cytokines [interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha]. Elevated levels of C3a and SC5b-9 were registered in filtered plasma, from the beginning of storage. C3a levels increased during storage. There was a higher rate of change during storage in C3a (P < 0.01) and SC5b-9 (P < 0.05) in plasma compared with filtered plasma. Interleukin (IL)-8 is released in whole blood. The cytokine levels generated in plasma and filtered plasma were low. Complement activation is present in whole blood, plasma and filtered plasma during storage. Prestorage filtration of plasma activates the complement cascade but does not influence cytokine generation.

Release of interleukin-10 by reinfusion of salvaged blood after knee arthroplasty.

OBJECTIVES: To determine whether the method of the autotransfusion in association with knee arthroplasty leads to differences in anti-inflammatory cytokines in the patient's circulation. DESIGN AND SETTING: Prospective study in a university hospital. PATIENTS: Twenty-one patients undergoing knee arthroplasty were randomized into two groups assigned to postoperative blood salvage. Seven patients received postoperatively filtered salvaged blood, and seven received centrifuged and washed salvaged blood. Patients with postoperative blood loss less than 400 ml (n=7) did not receive any transfusion. MEASUREMENTS AND RESULTS: Plasma levels of interleukin (IL) 1beta, IL-4, and IL-10 and of polymorphonuclear leukocyte elastase were measured by enzyme-linked immunosorbent assay. The plasma concentration of IL-10 was elevated after reinfusion of salvaged blood in all groups 1 day after surgery (p<0.05). Plasma IL-6, IL-10, and PMN elastase was higher (p<0.01) in all groups 1 day after surgery than preoperatively. There were significantly higher plasma levels 1 min after retransfusion of IL-6 (p<0.01) and IL-10 (p<0.05) in patients receiving filtered blood than in those receiving centrifuged and washed salvaged blood. CONCLUSION: Total knee arthroplasty results in the release of interleukin-10. Transfusion of filtered salvaged blood leads to higher levels of cytokines IL-6 and IL-10 than after transfusion of washed and centrifuged salvaged blood.

Complement split products and pro-inflammatory cytokines in salvaged blood after hip and knee arthroplasty.

PURPOSE: To determine whether salvaged autologous blood collected postoperatively contains complement split products (SC5b-9), and pro-inflammatory cytokines (IL-6 and IL-8) and whether there are any differences between blood collected during hip or knee surgery. METHODS: Fifty-eight consecutive patients undergoing hip or knee replacement surgery were studied. Thirty-eight had postoperative bleeding large enough to require infusion of salvaged blood. The salvaged blood was filtered during collection through a 200 microm filter and before infusion a 40 microm filter was used. Samples for complement and cytokine determinations were drawn from the circulation and from the collected blood. RESULTS: High concentrations of SC5b-9, IL-6, and IL-8 were found in salvaged blood. The concentrations were higher than in the circulation (P < 0.05). The circulating concentrations of IL-6 and IL-8 were increased 60 min and 12-18 hr after transfusion. There were no differences regarding SC5b-9, IL-6, and IL-8 in the blood collected after hip or knee surgery. CONCLUSION: Blood collected from a surgical wound contains large concentrations of inflammatory mediators. There were no differences between blood collected during hip or knee surgery.

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.

Effects on complement activation of a new continuous autotransfusion system.

Allogeneic blood transfusions may subject patients to risks of infection and allergic reactions. Various techniques for transfusion of shed blood have been developed. The aim of this study was to evaluate a new continuous autotransfusion system (Fresenius CATS) as regards its impact on the complement system, and on erythrocytes and leucocytes. Eighteen consecutive patients undergoing hip replacement surgery were studied. Complement variables (C4d, factor Bb, C3a and terminal complement complex, SC5b-9) and free haemoglobin, haemoglobin, leucocytes, platelets, albumin and protein were determined in the patient's blood preoperatively, 1 min before the start of transfusion, 15 and 60 min after transfusion; and in the reservoir, in the waste bag and in the retransfusion blood. Increased concentrations of C3a and SC5b-9 were found in the collected reservoir blood (P < 0.05). The washing and centrifugation procedure reduced these concentrations (< 0.001). High levels of free haemoglobin were found in the collected blood as well as in the processed product. The median haemoglobin level in the processed blood was 260gL-1 (range 104-289gL-1). Inflammatory mediators from the complement cascade are removed by continuous autotransfusion technique. The processed blood contains high levels of free haemoglobin.

Evaluation of tissue trauma after laparoscopic and abdominal hysterectomy: measurements of neutrophil activation and release of interleukin-6, cortisol, and C-reactive protein.

BACKGROUND: Trauma and major surgery stimulate a cascade of events that mediate the inflammatory response. The aim of our study was to determine whether or not hysterectomy leads to release of cytokines, cortisol, and C-reactive protein (CRP), activation of neutrophils, and activation of the complement cascade. A further aim was to compare laparoscopic and abdominal hysterectomy with regard to the same parameters. STUDY DESIGN: Twenty-four consecutive patients were randomized to either abdominal (n = 12) or laparoscopic hysterectomy (n = 12). Blood samples were drawn preoperatively, intraoperatively, and then at one minute, 24 hours, and seven days postoperatively. Interleukin-6 (IL-6) levels were used to evaluate cytokine release, cortisol and CRP to evaluate the inflammatory response, and polymorphonuclear (PMN) elastase to detect neutrophil activation. To evaluate complement activation, the terminal C5b-9 complement complex (TCC) was determined. RESULTS: Interleukin-6 concentrations were significantly elevated one minute and 24 hours postoperatively in both groups. Independent of the surgical technique or operative time, the highest IL-6 concentration was reached four hours after beginning the operation. Cortisol levels were significantly elevated during and after the operation in both groups. C-reactive peptide levels were significantly elevated in both groups 24 hours and seven days after the operation. Polymorphonuclear elastase was elevated 24 hours postoperatively in both groups. There were no signs of complement activation during the operative period or postoperatively in either patient group. CONCLUSIONS: Our results indicate serious tissue trauma during both laparoscopic and abdominal hysterectomy. The extent of surgical trauma did not differ between the two operative methods.

Formation of cytokines by retransfusion of shed whole blood.

We have studied, in 10 patients undergoing hip replacement surgery, the release of cytokines (tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-alpha), interleukin-1 beta (IL-1 beta), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in association with retransfusion of autologous shed blood. The patients were reinfused with whole blood collected after operation. The median volume returned to the patients was 300 ml whole blood (25-75% range = 300-425 ml). Before reinfusion, blood was filtered. Plasma concentrations of IL-6 increased 1 and 60 min after retransfusion (P < 0.05). The plasma concentrations of TNF-alpha, IL-1 alpha, IL-1 beta, IL-4 and IL-8 did not change significantly after retransfusion of shed wound blood. However, there were increased concentrations of IL-1 alpha, IL-1 beta, IL-6 and IL-8 in the collected blood (P < 0.001). The filtration procedure did not reduce significantly the concentrations of these factors. This study shows that whole blood collected from a surgical wound contains large concentrations of cytokines. Filtration of the shed wound blood did not reduce significantly these levels and retransfusion caused increased plasma concentrations of IL-6.

Complement, neutrophil, and macrophage activation in women with severe preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelet count.

Activation of complement, neutrophils, and macrophages was studied in 14 women with severe preeclampsia, 11 of whom had the syndrome of hemolysis, elevated liver enzymes, and low platelet count; in 14 women with normal pregnancies; in seven normal pregnant women undergoing cesarean deliveries; and in 15 healthy nonpregnant women. Activation of complement, neutrophils, and macrophages was measured by plasma determinations of complement split products, polymorphonuclear (PMN) elastase, and neopterin, respectively. Women with severe preeclampsia had increased levels of C5a, terminal complement complex, PMN elastase, and neopterin at delivery and 1 day postpartum as compared with the normal pregnant group. One week postpartum, neopterin remained higher in preeclamptic women, whereas the complement components and PMN elastase had returned to normal. Cesarean delivery after normal pregnancy did not increase the levels of complement split products, PMN elastase (except for one value), or neopterin. The nonpregnant women had normal PMN elastase and neopterin levels. Accordingly, complement, neutrophils, and macrophages are activated in women with severe preeclampsia at delivery. The plasma levels of PMN elastase correlated positively to the formed terminal complement complexes in vivo. An in vitro study was performed to elucidate further the connection between complement and leukocyte activation. Recombinant C5a incubated in whole blood and in a neutrophil cell suspension gave a dose-dependent release of PMN elastase. Both the clinical and the in vitro results indicate that activation of the complement system may affect the function of neutrophils. This study supports the theory that the pathologic manifestations of severe preeclampsia may be explained by complement-induced release of biologically active substances from activated leukocytes.