The effect of single dose versus two doses of praziquantel on Schistosoma haematobium infection and pathology among school-aged children in Mali.

The aim of this study was to assess the effect of two doses of 40 mg/kg praziquantel with 2 weeks interval versus a standard single dose of 40 mg/kg on cure rates, egg reduction, intensity of infection, and micro-haematuria in Schistosoma haematobium infections. A randomised controlled intervention study was carried out among school-aged children in two different endemic settings with follow-up at 3, 6 and 18 months following drug administration. Differences in cure rates between the two treatment regimens were not significant. However, in high transmission areas, the double treatment regimen was more effective in egg reduction than single treatment regimen and the difference in egg reduction between the two treatments was significant at 3 months (P<0.005), 6 months (P<0.0001) and 18 months (P<0.003) after treatment. There was a significant difference in the effect of the two treatments on prevalence of micro-haematuria at 18-month follow-up in both Koulikoro (P<0.001) and Selingue (P<0.003). The study shows that although no significant difference could be observed in the overall cure-rates between the two treatment regimens, the effect of double treatment was a significant reduction in infection intensity as well as micro-haematuria which may have a great impact in reducing subtle morbidity.

Circulating fibrosis markers, eosinophil cationic protein and eosinophil protein X in patients with Wuchereria bancrofti infection: association with clinical status.

We measured the concentrations of several circulating fibrosis markers (type I collagen I, type III procollagen, hyaluronan) and eosinophil granule proteins (ECP and EPX) in lymphatic filariosis patients to investigate their relationship with clinical, parasitological and immunological data. This study was conducted in Polynesian patients with various stages of the disease (acute lymphangitis, chyluria, hydrocoele, elephantiasis), a closely related microbial lymphangitis and endemic controls. We observed modifications of the different markers in this pathology. Serum type I collagen and PIIINP were decreased. Serum hyaluronan, linked to perilymphatic granulomatous inflammation, was significantly increased in acute lymphangitis and elephantiasis patients. Serum ECP was also increased, at the limit of significance in our sample, in elephantiasis patients. These two last markers, already validated in another helminth disease, schistosomiasis, have potential interest in terms of follow-up of morbidity in these parasitic diseases.

Assessment of eosinophil cationic protein as a possible diagnostic marker for female genital schistosomiasis in women living in a Schistosoma haematobium endemic area.

Eosinophil cationic protein (ECP) levels were measured in vaginal lavage extracts from 518 Zimbabwean reproductive women, age range 15-49 years, to assess the potential use of ECP as a diagnostic marker for female genital schistosomiasis (FGS). One hundred and fifty women had confirmed FGS status. These included 77 (cases) women who had ova in genital tissue and 73 (controls) women who had no ova in genital tissue. Participants were examined at baseline, 3 and 15 months post-treatment with praziquantel. ECP levels were determined using the enzyme linked immunosorbent assay (ECP-ELISA). ECP levels from 18 Norwegian women were used to calculate the diagnostic values of the test. FGS was diagnosed from the study population using genital biopsy and smears. Women were also diagnosed for urinary schistosomiasis using the urine filtration technique. The prevalence of urinary schistosomiasis was 39 % at baseline and this declined to 8% and 6% at 3 and 15 month post-treatment surveys, respectively. There was a higher mean ECP level in women with FGS, 889.3 ng/mL (95% CI: 457.0-1327.5) compared to the endemic control group, 359.1 ng/mL (95%, CI: 227.3-490.9), P = 0.027. Mean ECP levels declined at 3 months following treatment of infected individuals. There was no correlation between ECP levels and tissue ova density, and urine egg intensity. The sensitivity, specificity, positive and negative predictive values for the ECP-ELISA test were 35%, 80%, 65% and 53%, respectively. Our results indicate that FGS causes an inflammatory immune response that increases ECP levels in genital fluid. Treatment of schistosomiasis results in a regression of pathology and a decline in ECP levels. However, other factors such as allergy and microbial infection could also be responsible for increased ECP levels in genital mucosa. These conditions will affect the validity of the test in diagnosis of FGS.

CGRP-immunoreactive nerves in prurigo nodularis--an exploration of neurogenic inflammation.

BACKGROUND: The present study has explored the localization and distribution of calcitonin gene-related peptide (CGRP)-immunoreactive (IR) nerve fibers in prurigo nodularis, especially emphasizing its relationships to mast cells and eosinophils, which all are important contributors to inflammation. METHODS: The exact localization of CGRP in the nerve fibers of prurigo nodularis lesional skin has been clarified by an ultrastructural immunogold labelling technique; and the relationships of CGRP-IR nerve fibers to tryptase-IR mast cells or eosinophil cationic protein (ECP)-IR eosinophils were also investigated by immunofluorescence double-labelling. RESULTS: This ultrastructural study has demonstrated that CGRP immunoreactivity is increased in the dense-core vesicles in the axons of the prurigo nodularis lesional skin; the axons which contain CGRP are, in addition, enlarged and have more dense-core vesicles than the axons which do not contain CGRP. The immunofluorescence investigation demonstrated that tryptase-containing mast cells and ECP-containing eosinophils also are significantly increased in the lesional skin. CONCLUSIONS: The results indicate that certain neurons increasingly express CGRP, which may dynamically result in a neurogenic inflammation in the lesional skin, through vasodilatation, and recruitment and regulation of inflammatory cells, e.g. eosinophils and mast cells.

Quantitative assessment of eosinophiluria in Schistosoma haematobium infections: a new marker of infection and bladder morbidity.

Eosinophiluria, as quantified by measuring eosinophil cationic protein (ECP) in urinary extracts, microhematuria, egg excretion, and ultrasound-detectable bladder pathology were recorded in Schistosoma haematobium-infected Tanzanian school children at a baseline survey and during an 18-month post-treatment follow-up study. Significant correlations were seen between urinary ECP levels, intensity of infection, and bladder pathology. Treatment resulted in a marked reduction in prevalence and intensity of infection, in a delayed and less marked reduction in ECP levels, and in a resolution of pathology. The overall diagnostic efficiency of the ECP test (cut-off value for the ECP > or =5 ng/ml) in relation to infection was comparable with that of egg count and microhematuria, but with a better sensitivity than a single egg count. In relation to bladder pathology, the diagnostic performance of the ECP test (cut-off value for the ECP > or =25 ng/ml) exceeded that of a single egg count. In addition, the ECP was better in discriminating between different grades of bladder pathology. The present study points to the ECP as a useful marker of both S. haematobium infection and of associated bladder morbidity reflecting the inflammatory status of the bladder wall.

Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis.

BACKGROUND: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity of various paraclinical parameters in the diagnosis of ABPA in patients with CF. METHODS: Accumulated data from a 5-year period in 238 CF patients were used to divide patients into two groups designated the ABPA group (n=26) and the non-ABPA group (n = 35). Patients in both groups were colonized with Aspergillus fumigatus (Af.), but only the ABPA group consistently demonstrated specific IgE antibodies and specific precipitins. Patients without A. fumigatus colonization were not assigned to either of these groups (n = 177). By this selection as the true diagnosis, 10 patients were selected from the ABPA group and 10 patients from the non-ABPA group. RESULTS: The groups were comparable as to age, sex, lung function (P=0.6), and presence of chronic Pseudomonas aeruginosa infection (P>0.1). No significant difference between the groups in unspecific atopic parameters such as eosinophil count (P=0.9) or eosinophil cationic protein (ECP) in sputum, plasma, or serum (P=0.9, P=0.59, and P = 0.9, respectively) was demonstrated. Total IgE was significantly higher in the ABPA group (P<0.01). The groups were comparable in skin prick test (SPT) positivity to a standard panel of aeroallergens (pollen, dander, molds, and mites) (P>0.2). Statistically significantly higher levels in the ABPA group were demonstrated in specific IgE to Af. (P < 0.05), SPT positivity to Af. (P < 0.02), and Af. precipitins (P < 0.05). Histamine release (HR) to Af. tended to be higher (P=0.075) in the ABPA group. Specific IgE to Af. was determined by Magic Lite (ML), CAP, and Maxisorp (in-house RAST). The CAP level was one to two classes higher than the ML level; however, the results were comparable (r=0.66, P<0.005). IgE to Af. measured by CAP was the test which offered the highest positive predictive value (PPV) and negative predictive value (NPV). Optimal diagnostic cutoff levels for the diagnosis of ABPA were determined: class 2 for HR to Af., 200 kIU/l for total IgE, and 3.5 (titer) for precipitating antibodies to Af., and class 2 for IgE to Af. (by CAP System). CONCLUSIONS: Unspecific atopy markers were of limited value for the diagnosis of ABPA. Patients with ABPA do not seem to be more atopic to other aeroallergens than non-ABPA patients. The most valid parameters for the diagnosis of ABPA in CF are SPT to Af., IgE to Af. in combination with precipitating antibodies to Af., and/or total IgE.

Prestorage leukocyte filtration may reduce leukocyte-derived bioactive substance accumulation in patients operated for burn trauma.

Adverse effects of perioperative blood transfusion appear to be storage-time-dependent and may be related to extracellular accumulation of bioactive substances in blood products. In this study the clinical effects of leukofiltered and non-filtered blood products in patients undergoing surgery for burn trauma are investigated. 24 consecutive patients were randomly selected to receive transfusion with non-filtered blood components (group A, n = 12) or similar products, which were prestorage leukofiltered (group B, n = 12). The burn injury was scored using the Bull and Fischer index of age and burn surface area. Histamine, interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were analysed in plasma or serum collected from all patients 30 min before skin incision, at skin incision and 5, 10 and 30 min and thereafter every 30 min after skin incision until the grafts were secured by wrapping. Samples were also taken 8 h after skin incision and in the morning of postoperative days 1-5. The amount of blood products transfused from admission until day 5 postoperatively was recorded. All patients were followed until discharge or death. The Bull and Fischer index was comparable in the two groups. Prestorage leukofiltration reduced the amount of blood products required for transfusion significantly (p < 0.05) compared with non-filtered products. The levels of the various bioactive substances changed during and after the operation. In particular, ECP and MPO levels increased significantly (p < 0.05) in group A patients compared with unchanged (ECP) or decreased (MPO) levels in group B patients. IL-6 analyses showed, that the trauma had more severe impact on group B patients than on group A patients. Nevertheless, 4 patients died in group A and 2 in group B; all with a Bull and Fischer index between 1.0 and 2.0. Prestorage leukocyte filtration may reduce transfusion related accumulation of various bioactive substances and the requirement for blood in burn trauma patients.

Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue.

Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours, but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification. In the present study, the prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed. Intra-operative tumour tissue samples from 584 patients undergoing elective surgery for colorectal cancer were included. None of the patients received pre- or post-operative adjuvant chemotherapy. Tissue blocks were cut from the periphery of the tumours and embedded in paraffin. All blocks included both tumour tissue and normal bowel tissue. Serial sections of 4 microm were analysed for tumour tissue inflammatory cell infiltration using a computer- and video-assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used to dichotomize the cell counts with respect to survival. The median observation period was 61 (49-75) months. In a multivariate analysis including Dukes' stage, gender, age, peri-operative blood transfusion, tumour location, and counts of specific inflammatory cells, only advanced Dukes' stage ( p< 0.0001), high age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth.

Increased eosinophil activity in acute Plasmodium falciparum infection--association with cerebral malaria.

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8-10.7 ng/ml)) than in SA (4.7 ng/ml (3.0-7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6-5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.

Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Psuedomonas aeruginosa infection.

The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment consisted of budesonide dry powder, 800 microg twice daily, delivered from a Turbuhaler. The study period covered two successive 3-mo intervals between elective courses of intravenous anti-Pseudomonas antibiotics. Fifty-five patients entered the study, with a mean age of 20 yr and a mean FEV1 of 63% of predicted. Analysis of all patients entered, irrespective of trial adherence ("intention to treat"), showed a decrease in FEV1 in the first period of -0.032 L in patients on budesonide versus -0.187 L in patients on placebo (p = 0.08). The corresponding figures for the patients adhering to the protocol during the first period were -0.017 L versus -0.198 L (p < 0.05, confidence interval of the difference: -0.035 to +0.327 L). For all patients entered, as well as for patients adhering to the trial, there was always a trend in favor of budesonide, as judged by changes in FEV1 and FVC in both 3-mo periods. None of the patients had asthma, but the patients on budesonide had a mean improvement in histamine reactivity of +1.15 dose steps over the entire 6-mo period, as opposed to +0.017 dose steps in patients on placebo (p < 0.05). There was also a significant (p = 0.01) correlation between pre-trial histamine reactivity and the change in FEV1 in the first period in patients on budesonide. We conclude that inhaled glucocorticosteroids can be of short-term benefit in patients with CF and chronic P.a. infection and that those patients most likely to benefit from this treatment are patients with hyperreactive airways. Prolonged studies in larger number of patients are necessary to determine the long-term efficacy of this treatment.

Leucocyte and platelet-derived bioactive substances in stored blood: effect of prestorage leucocyte filtration.

Adverse reactions to transfusion of allogeneic blood may depend on content of leucocytes and platelets and on storage-time of the erythrocyte suspensions. Therefore, we studied the efficacy of prestorage leucocyte reduction by filtration on total content and extracellular accumulation of histamine, eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO), plasminogen activator inhibitor type-1 (PAI-1) and interleukin-6 (IL-6) in samples obtained from 5 units of SAGM blood, 7 units of plasma-reduced whole-blood and 6 units of whole-blood before and after filtration, respectively. In addition, we analysed supernatants from the same units after storage at +4 degrees C for 0, 21 and 35 d, respectively. The filtration was performed at room temperature within 2-4 h after donation. The substances were analysed by ELISA and RIA methods and we also analysed the donor plasma levels of the same bioactive substances. The total content of histamine, ECP, EPX, and MPO were 10-70-fold higher in all unfiltered erythrocyte products compared to donor plasma concentrations, while PAI-1 content was 15-20-fold higher only in plasma-reduced whole-blood and whole-blood. Prestorage leucocyte filtration significantly reduced the total histamine, ECP, EPX, MPO and PAI-1 content to levels similar to donor plasma levels in plasma-reduced whole-blood and whole-blood, while PAI-1 was still low in filtered SAGM blood. In addition, the levels of extracellular bioactive substances at d 0 after donation and filtration were within the range of concentrations in donor plasma, and there was no time-dependent accumulation during storage for 35 d at +4 degrees C. IL-6 was not detected in either plasma or samples obtained from the blood bags. These results suggest prestorage leucocyte filtration to deplete leucocyte contents to levels, which prevent the previously shown time-dependent accumulation of leucocyte derived bioactive substances in various erythrocyte suspensions. In addition, the PAI-1 results suggest leucocyte filters to reduce the obligatory platelet content in whole-blood products.

Bioactive substance accumulation and septic complications in a burn trauma patient: effect of perioperative blood transfusion?

Evidence has emerged that suggests adverse effects to perioperative homologous blood transfusion are related to the age of the blood products. Recently, time-dependent accumulation of bioactive substances in red cell suspensions, standard platelet concentrates and fresh frozen plasma during storage have been shown. The potential adverse effects of these bioactive substances were analysed in a burn trauma patient. A patient with 40 per cent second and third degree burn trauma without other injuries underwent a two-step transplantation operation. Samples for analyses of histamine, eosinophil cationic protein (ECP), eosinophil protein X (EPX), neutrophil myeloperoxidase (MPO) and interleukin 6 (IL-6) were drawn frequently from the patient before, during and after the operations, and from all transfused red cell, platelet and fresh frozen plasma units. Urine was sampled every hour during the first operation for analyses of ECP and EPX excretion. All analyses were performed by ELISA and RIA methods, and results compared to patient outcome. The patient received a total of 48 and 8 SAGM blood, 6 and 0 platelet and 12 and 4 fresh frozen plasma units at the two operations, respectively. Transfused products contained a total of 64.54 nmol and 17.50 nmol histamine, 115518 ng and 25764 ng ECP, 174457 ng and 38770 ng EPX, 6950915 ng and 1505125 ng MPO, and 14740 pg and 5600 pg IL-6 at the two operations, respectively. The accumulation of the substances in patient plasma correlated to postoperative septic reactions, without any disclosure of bacteraemia after the first operation, while the accumulation at the second operation correlated to the septic reaction and Pseudomonas aeruginosa infection. Time-dependent accumulation of bioactive substances in blood products during storage may be related to the development of post-transfusion adverse effects.

Diagnosis of female genital schistosomiasis by indirect disease markers: determination of eosinophil cationic protein, neopterin and IgA in vaginal fluid and swab eluates.

Based on assumptions about the pathophysiology of egg-related lesions in the lower reproductive tract, putative indirect disease markers were investigated in vaginal fluids from 54 Malawi adolescent girls and women infected with S. haematobium. These women received a careful gynecological examination during which biopsies were taken from the cervix, and, if present, also from suspicious lesions in the vagina and the vulva. If the biopsies, either in wet crushed preparations or in histological sections, contained eggs the patients were considered to have female genital schistosomiasis (FGS; n = 33). The remainder (n = 21) were classified as having urinary schistosomiasis only. Eosinophil cationic protein (ECP), a cytotoxic granule protein of eosinophils, neopterin, a second messenger molecule generated during the activation of macrophages, and IgA as an indicator of local B-cell activation were quantitatively determined in vaginal fluid. To clarify the origin of ECP, this protein was also looked for in histological sections by an immunohistochemical method. In order to explore whether such disease markers can be detected after absorption to a tampon-like material, ECP and IgA were also assessed after elution from a non-porous, polypropylene fibre web impregnated with vaginal fluid. The concentration of ECP in vaginal fluid and the degree of immunohistochemical staining in histological sections were significantly higher in patients with FGS than in women with urinary schistosomiasis only. The amount of ECP detected in histological sections correlated to the number of eggs/mm2 of compressed genital tissue (rho = 0.36, P = 0.02), and the concentration of ECP in vaginal fluid correlated to the concentration of neopterin as well as to that of IgA (rho = 0.52, P = 0.004 and rho = 0.37, P = 0.02, respectively). Median neopterin concentration in vaginal fluid was also higher in the FGS group, but the difference was not statistically significant. ECP could also be detected in eluates from impregnated fibre webs, but the concentration was approximately one power of 10 less than in the original vaginal fluid. These results demonstrate that indicators of immunological mechanisms related to the egg-granuloma might be useful as indirect disease markers for women with FGS if assessed in vaginal washings or swab eluates.

Reversibility of lower reproductive tract abnormalities in women with Schistosoma haematobium infection after treatment with praziquantel--an interim report.

Little is known whether and to what extent antiparasitic treatment cures female genital schistosomiasis (FGS). Using a standard protocol, of twenty-one women with FGS nine were re-examined at two to nine weeks after they had been treated with praziquantel at a single dose of 40 mg/kg. Symptoms related to pathology of the urinary tract and to a lesser extent of genital pathology subsided in most patients. Schistosoma haematobium ova were no longer detectable in urine of any of the patients post-treatment. Efficiency of chemotherapy against adult worms was confirmed by the disappearance of circulating anodic antigen (CAA) in serum. Sandy patches showed resolution in two of four cases after chemotherapy. Papillomata due to schistosomiasis alone improved, but persisted in mixed infection with human papilloma virus (HPV) or when HPV was the only underlying cause. In one patient ulcera could not be related with certainty to schistosomiasis at admission, but resolved after treatment with parziquantel. Leukoplakia (two cases) was not influenced by chemotherapy, or even increased during follow-up, regardless of whether ova had been detected or not. Although the follow-up period was rather short, time intervals were not standardized, and a relatively small number of patients was investigated, it could be shown that genital pathology due to sequestered S. haematobium ova is, at least partially, reversible already two to nine weeks after killing the adult worms by praziquantel. This is paralleled by a normalization of inflammatory immune responses detectable in histological sections and vaginal lavage.

Time-dependent, spontaneous release of white cell- and platelet-derived bioactive substances from stored human blood.

BACKGROUND: The mechanisms of the detrimental effects of perioperative allogeneic blood transfusion are still unclear. Previous studies have suggested a higher incidence of adverse effects after the use of blood stored for prolonged time. Therefore, a possible time-dependent release of various white cell- and platelet-derived bioactive substances in stored human red cell suspensions was studied. STUDY DESIGN AND METHODS: Whole blood (6 units), plasma-reduced whole blood (6 units), and saline-adenine-glucose-mannitol blood (6 units) from 18 unpaid, normal blood donors were stored under standard blood bank conditions at 4 degrees C for 35 days. After refrigeration, samples were collected from all blood bags on Days 0, 2, 5, 9, 14, 21, 28, and 35 of storage. Extracellular concentrations of eosinophil cationic protein, eosinophil protein X, plasminogen activator inhibitor 1, myeloperoxidase, and interleukin 6 were analyzed by enzyme-linked immunosorbent assay and radioimmunoassay. The total intracellular and donor plasma levels of these substances also were analyzed at the time of blood donation. RESULTS: Eosinophil cationic protein, eosinophil protein X, and myeloperoxidase increased 10- to 25-fold (p < 0.05) in a time-dependent manner in whole blood, plasma-reduced whole blood, and saline-adenine-glucose-mannitol blood during storage for 35 days. Plasminogen activator inhibitor 1 increased threefold to sixfold (p < 0.05) in whole blood and plasma-reduced whole blood, but not in saline-adenine-glucose-mannitol blood. Interleukin 6 was not detected in either plasma or samples obtained from the blood bags. CONCLUSION: Stored whole blood, plasma-reduced whole blood, and saline-adenine-glucose-mannitol blood may release white cell- and platelet-derived bioactive substances in a time-dependent manner, which may be related to the detrimental effects of perioperative blood transfusions. Therefore, prestorage white cell reduction should be considered for further improvement of red cell suspensions.

Biomolecular regulation of the IgE immune response III. Cytokine profiles in atopic dermatitis, inhalant allergy and non-allergic donors.

Cytokines-in particular interleukin 4 (IL-4), IL-5 and interferon gamma (IFN-gamma)-regulate both IgE synthesis and eosinophil activation in atopic diseases. To elucidate whether distinct profiles of cytokine production were related to serum level of IgE and eosinophilia, the spontaneous and inducible in vitro cytokine secretion from peripheral blood mononuclear cells (PBMC) was investigated. PBMC were isolated and cultured from three groups of donors: (1) patients with atopic dermatitis (AD) and high levels of serum IgE (> 5000 IU/ml, n = 11), (2) patients with diagnosed inhalant allergy (IA) and serum IgE in the range of 200-2000 IU/ml (n = 10), and (3) non-allergic individuals (NA) with serum IgE below 100 IU/ml (n = 10). The production of cytokines was determined in cultures after 24 h [IL-1 alpha, IL-4, IL-5, IL-6, tumour necrosis factor alpha (TNF-alpha), and TNF-beta] or 72 h (IL-2, IFN-gamma). The spontaneous production of IL-1 alpha was increased in the AD group compared to NA (P = 0.002), whereas for unstimulated cultures no other cytokine differed between patient groups. To identify conditions for optimal cytokine production, various combinations of phytohaemagglutinin (PHA), calcium ionophore (ION), and phorbol ester (PMA) were tested as stimuli. The combination ION + PMA induced the highest levels of IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha, whereas maximal production of IL-6 and TNF-beta were induced by PHA and PHA + PMA, respectively. The AD group demonstrated a significantly lower production of TNF-alpha and IFN-gamma compared with the two other groups, and IL-4 and IL-5 production increased in the IA group. The results suggest that in spite of the common features, i.e. raised serum IgE and eosinophilia, in IA and AD patients, the underlying aberrations in the cytokine network is different.

Plasma protein leakage and local secretion of proteins assessed in sputum in asthma and COPD. The effect of inhaled corticosteroids.

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation with cell infiltration, increased plasma exudation and abnormal local secretion of proteins. We have analysed whether sputum differs in this respect between asthma (n = 9) and COPD (n = 9), and whether inflammatory markers in sputum are affected by treatment. In non-smoking asthma patients there was more plasma protein leakage, based on the relative coefficient of excretion Q alpha 2macroglobulin/QIgG (P = 0.03). There was less local secretion of sIgA and lactoferrin than in COPD (P < 0.05). Tryptase was slightly higher in sputum from asthma than from COPD (P < 0.05), whereas eosinophil cationic protein and myeloperoxidase were similar. After treatment with glucocorticosteroids, there was a reduction in the Q alpha 2macroglobulin/Qalbumin (P < 0.015), but no effect was seen on the levels of products from local cells. We conclude that sputum analysis is useful to study the local inflammatory process in asthma and COPD.

Reduced cellular immune reactivity in healthy individuals during the malaria transmission season.

Antigen-induced cellular immune responses are suppressed during acute malaria. The present study engages the possibility that malaria-induced alterations in cellular immune reactivity extend beyond the clinical disease. Thus, lymphoproliferative responses of healthy individuals were diminished during the malaria transmission period in individuals living in an area of highly seasonal, unstable malaria transmission. This finding may have important implications for the design of studies of stimulatory properties of antigens using lymphocytes of endemic origin.