Complement activation capacity in plasma before and during high-dose prednisolone treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by intestinal inflammation mainly caused by a disturbance in the balance between cytokines and increased complement (C) activation. Our aim was to evaluate possible associations between C activation capacity and prednisolone treatment. METHODS: Plasma from patients with exacerbations of UC (n = 18) or CD (n = 18) were collected before and during high dose prednisolone treatment (1 mg/kg body weight) and tapering. Friedman's two way analysis of variance, Mann-Whitney U test and Wilcoxon signed-rank sum test were used RESULTS: Before treatment, plasma from CD patients showed significant elevations in all C-mediated analyses compared to the values obtained from 38 healthy controls (p < 0.02), and in mannan binding lectin (MBL)-concentration and MBL-C4-activation capacity (AC) values compared to UC patients (p < 0.02). Before treatment, plasma from UC patients showed significant elevations only in the classical pathway-mediated C3-AC compared to values obtained from healthy controls (p < 0.01). After treatment was initiated, significant reductions, which persisted during follow-up, were observed in the classical pathway-mediated C3-AC and MBL-C4-AC in plasma from CD patients (p < 0.05). CONCLUSION: Our findings indicate that C activation capacity is up-regulated significantly in plasma from CD patients. The decreases observed after prednisolone treatment reflect a general down-regulation in immune activation

Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis

publishedVersio

The asthma epidemic and our artificial habitats

BACKGROUND: The recent increase in childhood asthma has been a puzzling one. Recent views focus on the role of infection in the education of the immune system of young children. However, this so called hygiene hypothesis fails to answer some important questions about the current trends in asthma or to account for environmental influences that bear little relation to infection. DISCUSSION: The multi-factorial nature of asthma, reflecting the different ways we tend to interact with our environment, mandates that we look at the asthma epidemic from a broader perspective. Seemingly modern affluent lifestyles are placing us increasingly in static, artificial, microenvironments very different from the conditions prevailed for most part of our evolution and shaped our organisms. Changes that occurred during the second half of the 20th century in industrialized nations with the spread of central heating/conditioning, building insulation, hygiene, TV/PC/games, manufactured food, indoor entertainment, cars, medical care, and sedentary lifestyles all seem to be depriving our children from the essential inputs needed to develop normal airway function (resistance). Asthma according to this view is a manifestation of our respiratory maladaptation to modern lifestyles, or in other words to our increasingly artificial habitats. The basis of the artificial habitat notion may lie in reduced exposure of innate immunity to a variety of environmental stimuli, infectious and non-infectious, leading to reduced formulation of regulatory cells/cytokines as well as inscribed regulatory pathways. This could contribute to a faulty checking mechanism of non-functional Th2 (and likely Th1) responses, resulting in asthma and other immuno-dysregulation disorders. SUMMARY: In this piece I discuss the artificial habitat concept, its correspondence with epidemiological data of asthma and allergy, and provide possible immunological underpinning for it from an evolutionary perspective of health and disease

Enhancement of Leukocyte Membrane Receptor Expression after Mechanical Agitation

Granulocyte and lymphocyte suspensions were exposed to slight mechanical agitation for 30 s on a tube mixer before being examined for membrane receptors by rosette techniques. Agitation caused an increase in the proportion of granulocytes bearing receptors for sheep erythrocytes (E-R), for the Fc portion of IgG (Fc&lt;i&gt;γ&lt;/i&gt;-R), and for C3b (C3b-R), and of lymphocytes bearing the Fc&lt;i&gt;γ&lt;/i&gt;-R. The proportion of E-R-bearing lymphocytes was not enhanced, with the exception of the ‘early’ or ‘active’ E-R-bearing cells. The increase in rosette formation was specific, i.e. rosette formation with ox or rabbit E was not induced by agitation. The increased proportion of membrane receptors was not associated with an increase in granulocyte phagocytosis of preopsonized zymosan particles, as measured by chemiluminescence. Membrane perturbation thus probably increases the availability of surface receptors.</jats:p

Leukocyte Membrane Receptors in Meningitis and Other Bacterial Infections

Blood leukocytes from 37 patients with acute bacterial infections, and cerebrospinal fluid (CSF) granulocytes from 12 patients with bacterial meningitis, were examined for the distribution of membrane receptors (R) for (1) untreated sheep erythrocytes (E), (2) the Fc portion of IgG (Fc&lt;i&gt;γ&lt;/i&gt;), and (3) complement component C3b. We found a decreased percentage of granulocytes bearing Fc&lt;i&gt;γ&lt;/i&gt;-R in the CSF from patients with meningitis, and in blood from patients with respiratory tract infections. This group also had a decreased percentage of C3b-R bearing granulocytes on admission, whereas meningitis patients had lower levels of C3b-R and Fc&lt;i&gt;γ&lt;/i&gt;-R bearing granulocytes in the 2nd and 3rd week and even later. Several patients with meningitis and gastroenteritis had granulocytes bearing the E-R, previously considered specific for T lymphocytes. Such cells were also found in the CSF. Meningitis and respiratory tract infections were associated with a decreased percentage of ‘active’ T lymphocytes. The total percentage of T lymphocytes was also decreased in meningitis. Conversely the proportion of Fc&lt;i&gt;γ&lt;/i&gt;-R bearing lymphocytes (consisting mostly of B lymphocytes) was increased in most infections. During the first 3 weeks of bacterial meningitis, the percentages of Fc&lt;i&gt;γ&lt;/i&gt;- and C3b-R bearing granulocytes, and of Fc&lt;i&gt;γ&lt;/i&gt;-R bearing lymphocytes, gradually decreased, while the T lymphocyte percentage increased from the initial low values.</jats:p

Upper airway inflammation in waste handlers exposed to bioaerosols

Aims: To examine work associated upper airway inflammation in 31 waste handlers, and to correlate these findings with personally monitored exposure to different bioaerosol components. Methods: Cell differentials, interleukin 8 (IL-8), myeloperoxidase (MPO), and eosinophilic cationic protein (ECP) were examined in NAL (nasal lavage), and swelling of the nasal mucosa was determined by acoustic rhinometry before work start on Monday and the following Thursday. Bioaerosol exposure was determined by personal full shift exposure measurements on Monday, Tuesday, and Wednesday and analysed for total bacteria, fungal spores, endotoxin, and ß(1→3)-glucans. Results: The increased percentage of neutrophils from Monday (28%) to Thursday (46%) correlated with increases in ECP (r(S) = 0.71, p < 0.001) and MPO (r(S) = 0.38, p < 0.05), and showed a close to significant correlation with nasal swelling (r(S) = -0.55, p = 0.07). The Thursday levels of neutrophils, MPO, and IL-8 were associated with the exposure to fungal spores (range 0–2.0 x 10(6)/m(3)) and endotoxin (range 4–183 EU/m(3)) measured the day before, and the median exposure to ß(1→3)-glucans (range 3–217 ng/m(3)), respectively (r(S) = 0.47–0.54, p < 0.01). Swelling of the nasal mucosa was associated with the fungal spore and ß(1→3)-glucan exposure (r(S) = 0.58–0.59, p < 0.05). Conclusion: These results are based on a relatively small population, and conclusions must be drawn with care. The results suggested that a moderate exposure to fungal spores, endotoxins, and ß(1→3)-glucans during waste handling induced upper airway inflammation dominated by neutrophil infiltration and swelling of the nasal mucosa