Modulation of contact sensitivity in mice by interleukins.
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Publications and source records attributed to O Bäck.
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Iontophoresis was used to evaluate the peripheral reactivity of phenylephrine (alpha 1-agonist), isoproterenol (beta-agonist) and metacholine (cholinergic agonist) in patients with Alzheimer's disease (AD). The cutaneous responses--erythema and blanching--were visually recorded. Healthy personnel, medical students and patients with various dermatoses served as controls. A reduced response towards the adrenergic agonists was seen in AD. The reduced sensitivity was highly significant for the beta-agonist isoproterenol (p less than 0.001), in contradistinction the metacholine response did not differ between AD and age-matched controls. Furthermore, increasing age did not seem to significantly influence the cutaneous responses in mentally healthy controls. Thus, a reduced peripheral adrenergic reactivity was observed in the patients suffering from AD.
The efficacy of oral acyclovir in a twice-daily treatment regime was demonstrated in an open long-term study in 8 patients with frequently relapsing genital herpes type II infections. The treatment was well tolerated and no side effects were noted during the medication period of 6-21 months. No signs of decreased sensitivity for acyclovir appeared.
In patients with Pityrosporum folliculitis the mean serum antibody titer against Pityrosporum orbiculare was significantly higher than in healthy control subjects (p less than 0.01). The mean number of P. orbiculare organisms per square centimeter cultured from normal-looking skin in patients was not significantly higher than the number cultured from normal-looking skin in control subjects. Results of prick tests against P. orbiculare extract were negative or weak, indicating that patients with Pityrosporum folliculitis had no type I hypersensitivity against P. orbiculare. Immunohistochemical staining of skin lesions showed perivascular dermal cell infiltrates near the hair follicles dominated by anti-Leu 3a-reactive T lymphocytes. Human lymphocyte antigens with the DR locus, but not those with the DQ locus, on keratinocytes were observed in one case.
In the deteriorating group of sarcoidosis patients, progress towards pulmonary fibrosis is a major problem. In order to benefit from corticosteroids, it is important for the treatment to start early. We studied a group of 45 patients with sarcoidosis. Most of them were newly detected patients and none were under or had currently received corticosteroid therapy. The patients were followed for at least six months. We found that increased amounts of polymorphonuclear neutrophils (PMN) or lysozyme-positive macrophages (Lys+MF) and mast cells (MC) in bronchoalveolar lavage (BAL) could implicate a bad prognosis.
Thirty-three patients with frequently recurring genital herpes completed a randomized double-blind, crossover trial with oral acyclovir 200 mg 4 times a day and placebo for periods of 12 weeks. Five patients (15%) had full recurrence during acyclovir treatment and 31 (94%) while receiving placebo. The median time to first recurrence was 20 days for placebo and more than 84 days for acyclovir. It was concluded that acyclovir was well tolerated and an effective treatment to suppress the disease in selected cases of severe and frequently recurring genital herpes. However, the relapses seem to occur with the same rate as before, when the suppressive acyclovir treatment is stopped.
By means of a prospective study design and multivariate regression analyses we have studied the relative importance of atopy, metal dermatitis and earlier hand eczema as risk factors for the development of hand eczema in women during 20 months of "wet" hospital work. The population consisted of 1857 women. The prevalence of hand eczema during the observation period was 41%. The risk of developing hand eczema was calculated as predicted relative odds ratios. The interrelationship of the risk factors was analysed. A summarized description of this analysis shows that a history of earlier hand eczema increased the odds by 12.9 times, a history of metal dermatitis by 1.8 times and atopic dermatitis and atopic mucosal symptoms by 1.3 times. Thus a history of earlier hand eczema seems of crucial importance for the occurrence of hand eczema in women in 'wet' hospital work. Our hypothesis is that a history of earlier hand eczema may be considered a major indicator of a skin vulnerability factor predisposing the individual to hand eczema. If the hypothesis is true, this factor may be present approximately in one half of the subjects with atopic dermatitis, in one fourth of the subjects with atopic mucosal symptoms and in one fifth of the non-atopics.
The contact activation and fibrinolytic systems were assessed in 5 patients with hereditary angioedema (HAE). Reductions in F XII levels and increase in kallikrein-like activity in some patients indicated activation of the contact (intrinsic) system of coagulation. A great increase in plasmin-alpha 2-antiplasmin complex in all subjects indicated that in this disease, there is a constantly ongoing fibrinolysis. Since C1-inhibitor, the deficient protein in HAE, is a poor inhibitor of the well-known extrinsic (tissue-type) plasminogen activator, but the major inhibitor of the contact activation system and a related in vitro phenomenon termed intrinsic fibrinolysis, our data show that this fibrinolytic system is also sometimes operating efficiently in vivo. Furthermore, the known clinical data on HAE are compatible with a role of intrinsic fibrinolysis in the pathophysiology of this disease.
In preparations of papillary dermis taken from clinically normal skin of patients with dermatitis herpetiformis (DH), the disappearance of granular IgA deposits induced by peptic digestion was partial at pH 4.5 and total at pH 4.1, as visualized by immunofluorescence microscopy. In a model system in which human monomeric IgA was digested by pepsin using a pepsin-IgA ratio of 100:0.3, an IgA concentration of 3 lambda g/ml and a pH range of 5.1-4.1, the degradation of IgA molecules did not appear to proceed beyond the formation of fragments corresponding to F (ab)'. When supernatants after peptic digestion of papillary dermis at pH 4.1 were analysed by sodium-dodecylsulphate (SDS)-polyacrylamide gel electrophoresis after reduction and alkylation followed by electrophoretic transfer to nitrocellulose membranes and subsequent immunochemical detection, IgA-like material corresponding to the alpha-chain part of F (ab)' fragments was found in preparations from DH patients but not in those from controls.
Tetracyclines, especially doxycycline, have been reported to inhibit the in vitro migration of polymorphonuclear leukocytes (PMNs). Twelve healthy probands were treated with doxycycline 200 mg. No inhibition of PMN migration in a casein gradient was demonstrated 24 h later. It is suggested that the effect of oral treatment with doxycycline on PMN chemotaxis is negligible.
Fifty-one patients, thirty-nine women and twelve men, with Pityrosporum folliculitis are described. This investigation clearly demonstrates that Pityrosporum folliculitis is a real entity. The diagnosis is based primarily on the clinical picture, direct microscopy, histopathology, and the effect of antimycotic treatment. The typical patient is a woman of 30 years with itching follicular papules and pustules localized to the upper trunk or upper arms. Direct microscopy reveals round yeast cells and sometimes even hyphae. In biopsy specimens, abundant round budding yeast cells and occasionally hyphae are seen in a dilated follicle. Yeast growth is obtained only on lipid-enriched media. Twenty-five patients were treated with selenium sulfide shampoo, twelve with 50% propylene glycol in water, and ten with topical econazole cream with good results. Cure or marked improvement was seen after 3 to 4 weeks, but symptoms and lesions recurred if treatment was not continued intermittently. Predisposing factors such as occlusion and greasy skin are probably important, and future studies should focus on fungal hypersensitivity, quantitative variations in the number of Pityrosporum orbiculare, lipid composition of the skin, and extended epidemiologic data.
Granular deposits of IgA in radioactively labeled thin slices of papillary dermis from 4-mm punch biopsies of clinically normal skin from patients with dermatitis herpetiformis were solubilized with sodium dodecyl sulfate (SDS) or peptic digestion at pH 4.5. Solubilized IgA-like material was isolated by immunoprecipitation and analyzed by electrophoresis in one and two dimensions in polyacrylamide gels containing SDS followed by autoradiography. SDS extracts contained IgA-like components corresponding to monomers, dimers, as well as higher polymers of IgA. A fraction of the SDS-soluble material behaved like IgA upon immunoprecipitation but could not be deaggregated to alpha- and light chains by reduction and alkylation, suggesting that it was present as irreversible aggregates with itself or with other proteins. Peptic digestion at pH 4.5 released fragments which were precipitated by antibodies to human alpha-chains and had molecular weights similar to the proteolytic fragments corresponding to F(ab)2 and Fab formed by peptic digestion of human monomeric IgA under the same conditions.
A mouse model for assessment of the anti-inflammatory effect of topical glucocorticoids is described. Mice, sensitized to picryl chloride, had both ears painted with the sensitizer followed 2 hours later by the application of the topical steroid to one ear and the corresponding vehicle to the other. The contact sensitivity reaction, measured by swelling of the ear, was recorded 24 hours later. Dilutions of the steroid formulations inhibited the ear swelling in a manner related to dose-response. Suppression of the contact sensitivity reaction of the vehicle-treated ear as well was regarded as a systemic effect of the glucocorticoid. There seems to be a good correlation between the efficacy of the topical steroids assessed in this mouse model and the vasoconstrictor test on intact human skin.
An enzyme linked differential antibody immunosorbent assay for the quantitation of the C1s-C1 inhibitor complex has been developed. A study of the assays' performance under various conditions has shown that before use in the assay, it is imperative to remove competing forms of C1s from the samples to be tested. This is conveniently achieved in human plasma or serum by polyethylene glycol precipitation of the C1qrs, since the C1s-C1 inhibitor complex remains soluble and can be assayed in the supernatant solution. The detection limit of the assay in the plasma milieu is 0.1 mg/l, and the concentrations of the C1s-C1 inhibitor complex were found to be 1 mg/l in citrated plasma and 2 mg/l in serum. Activation of the fibrinolytic system in vivo does not seem to result in any appreciable C1 activation, since there was no concomitant major change in the plasma concentration of the C1s-C1 inhibitor complex.
In a previous study, polymorphonuclear (PMN) leukocyte chemotaxis in vitro was inhibited by therapeutic concentrations of griseofulvin. In the present investigation, PMN migration in a casein gradient was studied in a cell suspension containing serum collected before and after a therapeutic peroral single-dose of griseofulvin. The PMN migration in vitro was not influenced significantly by the presence of griseofulvin-containing serum. It is suggested that peroral griseofulvin treatment has negligible effect on PMN chemotaxis in vitro.
A technique has been devised to isolate the thin papillary part of the dermis from punch biopsies. Papillary dermis has been treated with various proteolytic enzymes in order to release or solubilize the granular IgA deposits from the papillary dermis of patients with dermatitis herpetiformis. Incubation of the thin skin preparations with pepsin caused a disappearance of the specific fluorescence with antibodies to human IgA. After peptic digestion small amounts of IgA could be detected in the supernatants. There was some evidence that this amount was larger for preparations from patients with dermatitis herpetiformis than from controls. Corresponding procedures with trypsin, collagenase, or elastase had no detectable effect on the IgA deposits. The experiments with elastase seemed to give support for previous reports on association between the granular IgA deposits and the microfibrils of elastic fibers.
The adrenoceptor-mediated responses in human skin (blanching and erythema) were studied by an iontophoretic technique. It is concluded that the receptors in superficial dermal blood vessels belong to the subclasses alpha 1 and beta 2.
Tetracyclines, and especially doxycycline, have been reported to inhibit polymorphonuclear leukocyte (PMN) migration. The effect of a therapeutic doxycycline concentration (4.33 micrograms/ml) on PMN migration in vitro was tested with the leading-front technique. No significant effect could be demonstrated on PMN chemokinesis and chemotaxis. It is thus concluded that the effect of therapeutic doxycycline concentrations on PMN migration is negligible. This conclusion has a bearing upon the choice of antimicrobial therapy.