I. van der Ploeg

Detection of Pityrosporum orbiculare reactive T cells from skin and blood in atopic dermatitis and characterization of their cytokine profiles

Background Atopic dermatitis (AD) is associated with increased levels of serum igE. and T‐helper (Th) cells are thought to a play role in the pathogenesis. Individuals with AD often develop IgE antibodies against the yeast Pityrosporum orhiculare. a member of the normal cutaneous flora.

No apparent association between periocular and ocular microcolonization and the degree of inflammation in patients with atopic keratoconjunctivitis

Background The cause of the chronic inflammation in atopic keratoconjunctivitis (AKC), the ocular manifestation of atopic eczema/dermatitis syndrome, is largely unknown.

IgE is expressed on, but not produced by, fetal cells in the human placenta irrespective of maternal atopy.

The prevalence of atopic diseases in children has increased during the last decades. Atopic symptoms usually appear early in life. This implies an early priming for atopic disease, possibly even at the fetal level. We therefore compared the presence and production of IgE in the local in utero environment during pregnancy in atopic and non‐atopic women. Eighty‐six women were included in the study. Fifty women were demonstrated to be atopics, based on clinical symptoms of atopic disease together with a positive Phadiatop and/or skin prick test. Placentas from these term pregnancies were obtained. Slices covering the full thickness of the placenta were cut clockwise around the umbilical cord and were analysed with immunohistochemistry. Surprisingly, numerous IgE+ cells, located primarily in the fetal villous stroma, were detected in a majority of the investigated placentas irrespective of the atopy of the mother or maternal or fetal total serum IgE levels. The placental IgE could not be demonstrated to be bound to IgE receptors, but was shown to be bound to fetal macrophages, possibly via FcγRI. No evidence was found for local fetal IgE production, although cells producing epsilon transcripts were occasionally detected in the decidua. We describe here the novel finding of numerous IgE+ cells in the human placenta, suggesting an hitherto unknown role for IgE in a successful pregnancy outcome, irrespective of whether or not the mother is atopic.

Similar T helper Th2‐like cytokine mRNA expression in vernal keratoconjunctivitis regardless of atopic constitution

Background: Many patients with vernal keratoconjunctivitis (VKC), a severe chronic allergic eye disease in children, exhibit IgE‐sensitization, but about 40% of cases lack this immunologic trait. As a disease factor in VKC, IgE is thus not fully understood. The aim of this study was to investigate whether there are any differences in the conjunctival cytokine messenger (m)RNA pattern related to IgE‐sensitization in children suffering from VKC.

Increased occurrence of IgE+ and FcεRI+ cells in adenoids from atopic children

Background: To examine the influence of atopy on the different cell populations in adenoids, we investigated the presence of IgE+ cells, cells expressing the high‐affinity receptor for IgE (FcεRI), and various other cell populations in adenoid tissue, in atopic and nonatopic children with otitis media with effusion (OME) or adenoid hyperplasia (AH).

The tryptase inhibitor APC-366 reduces the acute airway response to allergen in pigs sensitized to Ascaris suum

Background Tryptase is a mast cell serine protease that is released during mast cell degranulation. It has been implicated as an important enzyme in the pathophysiology of asthma, but its role in this disease is not fully elucidated.

Limited distribution of pertussis toxin in rat brain after injection into the lateral cerebral ventricles

In vivo administration of pertussis toxin is often used to study the involvement of guanine nucleotide binding proteins in signal transduction. Especially when it is administered in the brain the effect is often poor. This could be due to the fact that pertussis toxin does not reach the area of interest. To evaluate the extent to which pertussis toxin is distributed in rat brain after intraventricular injection, different techniques were used. Immunohistochemical studies with an antibody against pertussis toxin showed that immunoreactivity was limited to periventricular brain structures less than 0.5 mm from the lumen. The highest immunoreactivity was seen 16-24 h after injection. After 96 h the labeling was very weak. The proportion of guanine nucleotide binding proteins that were ADP-ribosylated by in vivo injection of pertussis toxin into the ventricles as assessed by in vitro [32P]-back-ADP-ribosylation was very low 48 h after the injection, in all regions studied. Direct injection of pertussis toxin into the brain caused a marked ADP-ribosylation localized to the region injected that was maximal at 72 h after injection. At 96 h there were also effects after control injections, indicating non-specific effects. Synaptosomal membranes and other membranes were equally affected by pertussis toxin. The results suggest that in studies regarding the effect of pertussis toxin treatment on signal transduction, the toxin must be injected very close to the brain region of interest and, furthermore, that the rats should be killed 48-72 h after injection. In case of lack of effect on the response of interest one should examine whether the ADP-ribosylation of pertussis toxin-sensitive guanine nucleotide binding proteins in the area of concern has been affected.

IL‐13 over‐expression in skin is not confined to IgE‐mediated skin inflammation

IL‐13 is produced by T cells and, like IL‐4, it can induce the production of IgE and IgG4. In order to investigate if IL‐13 is a specific marker for atopic dermatitis (AD), IL‐13 gene expression was analysed in chronic lichenified lesions and non‐lesional skin of patients with AD, in involved and non‐involved skin of patients with psoriasis, in positive tuberculin reactions in non‐atopics, and in the skin of healthy control subjects. Patients with AD (n = 9) showed sensitization to common air‐borne allergens (positive Phadiatop) and had total serum IgE values in the range from 10 to 4800 kU/l (median 170 kU/l ). Competitive reverse transcription‐polymerase chain reaction (RT‐PCR) was used to assess IL‐13 gene expression in skin biopsy specimens. IL‐13 gene expression was markedly higher in chronic lichenified lesions of patients with AD (P < 0.01), and in the positive tuberculin reactions (P < 0.01; n = 12) than in skin from healthy control subjects (n = 10). However, there was no significant difference in IL‐13 gene expression in the skin of patients with psoriasis (n = 10) and that of healthy control subjects. The dermal cell infiltrates were larger and the relative amount of CD3+ and CD4+ cells in these infiltrates was higher in the skin of subjects with a positive tuberculin reaction than in lichenified AD skin. However, these differences were not reflected in differences in IL‐13 gene expression. Different triggers of IL‐13 gene expression may influence the diverse patterns of inflammation seen in different inflammatory skin disorders.

Cytokine mRNA expression in patients with mild allergic asthma following low dose or cumulative dose allergen provocation

Background Allergen provocation is a very useful way to study the inflammatory response in asthmatic patients. Although cumulative dose regimens are most often applied, another provocation model with repeated inhalations of low doses of allergens has recently come into use.

Pertussis toxin treatment counteracts the cardiovascular effects of neuropeptide Y and clonidine in the awake unrestrained rat

The role of G-proteins in the mediation of the cardiovascular effects of neuropeptide Y and the alpha 2-adrenoceptor agonist clonidine was investigated by injections of pertussis toxin (10 micrograms/30 microliters, i.v.t., 24 h) in the awake unrestrained male rat. Treatment with pertussis toxin was found to inhibit the hypotensive and bradycardic actions of neuropeptide Y (1250 pmol) and the hypotensive actions of clonidine (1875 pmol). Control experiments showed that treatment with pertussis toxin caused an approximately 50% reduction in the back-ADP-ribosylation of GTP-binding proteins. These results suggest that G-proteins mediate the central cardiovascular actions of neuropeptide Y and clonidine.