Early cellular reactions induced by dinitrochlorobenzene in sensitized human skin

Serial biopsies during the first 24 hours after dinitrochlorobenzene (DNCB) challenge in fifteen sensitized patients have shown that DNCB associates with Langerhans cells within I hour of application, and has reached the dermis around the appendages by 6 hours.     

Lymphocyte timulation in the cellular inflammatory reaction of some human skin tumours

Summary By labelling dermal infiltrate cells with H3-thymidine, two types of skin tumours can be distinguished: one type with many labelled cells in the infiltrate (H3-thymidine labelling index, H3-I), the other with few labelled cells. Type I includes malignant melanoma (H3-I = 2.2%) and hemangioendothelioma (2.8%).Type II includes metastases of malignant melanoma (1%), squamous cell carcinoma (1.1%), basal cell epithelioma (0.5%), nevus cell nevus (0.6%), and nevoid lentigo (0.4%).The number of labelled cells in the cellular reaction of Type II tumours does not differ significantly from that in normal human corium (0.75%), though there may be a dense cellular reaction. DNA-synthesizing cells were classified with the aid of characteristical stainings and histochemical methods. A vast majority of them were found to be lymphocytes. Our research underlines the special importance of cellular inflammatory reaction, i.e. cellular immunity, in malignant melanoma and probably in hemangioendothelioma.

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Zusammenfassung Mittels H3-Thymidin-Markierung von dermalen Infiltratzellen lassen sich zwei Typen von Hauttumoren unterscheiden. Ein Typ mit zahlreichen markierten Zellen im Infiltrat (H3-Thymidin-Markierungsindex, H3-I), der andere mit wenigen markierten Zellen. Zu Typ I gehören das maligne Melanom (H3-I = 2,2%) und das Hämangioendotheliom (2,8%).Zu Typ II gehören Metastasen des malignen Melanoms (1%), Plattenepithelcarcinom (1,1%), Basaliom (0,5%), Nävuszellnävus (0,6%) und nävoide Lentigo (0,4%). Der Prozentsatz der markierten Zellen im Infiltrat der Gruppe II unterscheidet sich nicht signifikant von dem im normalen menschlichen Corium (0,75%), obwohl manche dieser Tumoren ein dichtes zelluläres Infiltrat aufweisen. Die DNS-synthetisierenden Zellen wurden mittels charakteristischer Färbungen und histochemischer Methoden differenziert und in weit überwiegender Zahl als Lymphocyten identifiziert. Unsere Untersuchungen unterstreichen die besondere Bedeutung der cellulärentzündlichen Umgebungsreaktion, d. h. der cellulären Immunreaktion, beim malignen Melanom und möglicherweise beim Hämangioendotheliom.

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We thank Prof. Dr. K. J. Lennartz and Mrs. E. Vierkotten, Institute of Pathology, University of Cologne, for their methodological and technical assistance.     

The role of ceramides in skin homeostasis and inflammatory skin diseases

Ceramides, members of sphingolipid family, are not only the building blocks of epidermal barrier structure, but also bioactive metabolites involved in epidermal self-renewal and immune regulation. Hence, abnormal ceramide expression profile is recognized to defect extracellular lipid organization, disturb epidermal self-renewal, exacerbate skin immune response and actively participate in progression of several inflammatory dermatoses, exemplifying by psoriasis and atopic dermatitis. Here, we discuss recent advances in understanding skin ceramides and their regulatory roles in skin homeostasis and pathogenic roles of altered ceramide metabolism in inflammatory skin diseases. These insights provide new opportunities for therapeutic intervention in inflammatory dermatoses.     

The role of basophils in inflammatory reactions.

This review demonstrates that basophils reflect skin and lung mast cell reactivity and show characteristic changes in mediator release associated with clinical disease. Although the numbers of IgE molecules and IgE receptors on basophils have been enumerated, these have, in most instances, little influence on the release of histamine after challenge. There is, rather, a parameter of "releasability" that may be a major variable in allergic disease states. Basophils contain and release histamine, the eosinophil chemotactic factor of anaphylaxis (ECFA), a slow reacting substance of anaphylaxis (SRS-A), and a kallikrein. The release process is controlled by hormone-basophil receptor interactions that determine the cyclic AMP level; plasma and tissue adenosine levels appear prominent in this control. Histamine feeds back to negatively modulate basophil and mast cell release through a specific histamine 2-receptor; it also inhibits lymphocyte and neutrophil function. Like neutrophils, basophils contain beta-glucuronidase while neutrophils contain SRS-A and a low-molecular-weight ECF. The stimuli for primary basophil and neutrophil release are, however, quite different, although phagocytic stimuli, which fail to cause basophil mediator release, potentiate the IgE response. It is concluded that basophols play a significant in vivo role in inflammation by acting as an interface between foreign antigens, the serum cascade systems, and other inflammatory cells.     

Asymmetry of cellular response as revealed by the skin window technique

Utilizing the skin window technique, symmetry of cellular response was examined by comparing cellular exudates from symmetrical areas of opposite forearms in eleven subjects. Testing the hypothesis that there would be no significant difference between symmetrical sites subjected to the same stimulus at the same time, the percentages of cell types in the cellular exudate were calculated for 126 paired comparisons. A significant difference in the cell types arriving at the skin window sites occurred in seventy-six out of the 126 paired comparisons (Chi square analysis, P<0.01). This lack of a symmetrical response could be due to an inherent variability of the cellular response or to an inability to manipulate the two sites in exactly the same manner. Although significant differences were found between the above individual matched pairs (Chi square analysis), the ‘t’ test analysis of the pairs grouped by hour revealed no significant difference in mean percentages of cell types between left and right arms at fourteen time intervals. Thus, previous skin window investigations comparing mean percentages of cell types were found to be valid, even though symmetry of cellular response in individual subjects is much less than expected.     

Prostaglandins, leukotrienes, anti-inflammatory substances and their importance in inflammatory reactions of the skin

Prostaglandins appear to play an important role as mediators of inflammation since they fulfill the major criteria. They possess powerful proinflammatory properties; they are present in increased concentrations in a wide range of proinflammatory lesions, and anti-inflammatory drugs inhibit their formation. The role of leukotrienes and other hydroxy fatty acid products is far less clear although their participation in cellular events seems probable. Steroid and nonsteroid anti-inflammatory drugs owe their activity at least in part to inhibition of biosynthesis of prostaglandins, although these two drug classes appear to act at different points in the pathways. It becomes increasingly clear that the oxygenation of arachidonic acid leads to the formation of a multiplicity of pharmacologically active fatty acids of which only a few have so far been identified.     

The inflammatory response to anthralin

The inflammatory dose-response of the skin to topical anthralin was measured in patients with psoriasis, and compared with the response in a group consisting of normal subjects and patients with unrelated skin diseases. Wide individual variation was demonstrated but there was no significant difference between individuals with and without psoriasis nor was there any significant association with age, sex, skin type and original thickness or cigarette smoking.     

Cutaneous responses to topical methyl nicotinate in human forearm and vulvar skin.

In order to identify and define differences in percutaneous absorption and microcirculatory sensitivity between forearm and vulvar skin we studied the response of human forearm and vulvar (labium majus) skin to topical methyl nicotinate (MN) in 11 healthy premenopausal volunteers. MN-induced erythema was assessed by laser Doppler velocimetry (LDV). The following parameters were compared: 1) basal cutaneous blood flow, 2) the time to peak response, 3) the magnitude of LDV peak response, 4) the area under the LDV response-time curve and 5) the decay time to 75% of peak response. Basal cutaneous blood flow at the vulva was higher than at the forearm (P less than 0.05); the magnitude of peak response was lower at the vulva than at the forearm (P less than 0.01); the area under the curve was lower at the vulva than at the forearm (P less than 0.001); the decay time to 75% of peak response was shorter at the vulva than at the forearm (P less than 0.001). The time to peak response showed no significant differences between sites. The results indicate that the MN-induced vasodilatation is less intense and lasts shorter in vulvar compared to forearm skin.     

The influence on the dermal cellular infiltrate of topical steroid applications and vehicles in guinea pig skin: normal skin, allergic and toxic reactions

The mechanisms of the anti-inflammatory effects of carticosteroids are uncertain but could be explained by an influence on infiltrating leukocytes. Our method for the qualitative and quantitative investigation of the dermal cellular infiltrate makes it possible to study the effects of topically applied corticosteroid preparations and vehicles on the infiltrating leukocytes of normal skin, allergic and toxic reactions in guinea pig skin. Ointment and cream vehicles as well as corticosteroid cream and ointment preparations often caused erythema and increased mononuclear infiltrate after only short periods of application (24-72 h). The strongest steroid ointment gave the most marked macroscopic response and propylene glycol preparations the most marked cellular response. In both toxic and allergic reactions, application of steroid preparations after the provocation gave no beneficial result cither macroscopically or microscopically. Macroscopic scores were worsened by cream and ointment preparations. Although steroid solutions had no beneficial effect, they caused no detrimental effect. The guinea pig seems to be extremely sensitive to irritants and has not proved to be a suitable model for this approach to the study of the efficacy of topically applied steroids.     

抗白三烯药物在炎症性皮肤病中的应用

白三烯(leukotriene,LT)是重要炎症递质,参与多种皮肤病的发生、持续和发展.该文对LT在炎症性皮肤病发病中的作用和抗白三烯药物在该类皮肤病中的临床应用作一概述.     

Biological response modifiers and their potential use in the treatment of inflammatory skin diseases

In recent years, a more detailed understanding of the pathogenesis of several inflammatory skin diseases, combined with the developments within biotechnology, has made it possible to design more selective response modifiers. Biological response modifiers hold the potential for greater effectiveness and fewer side-effects than the current systemic therapies now used for severe psoriasis, contact dermatitis and atopic dermatitis. In the pathogenesis of inflammatory skin diseases, the immune system plays a pivotal role, and this is where biological response modifiers such as monoclonal antibodies, recombinant cytokines, or fusion proteins may be effective. Several biological response modifiers have already shown positive results in phase II/III clinical trials in skin diseases, and many new biological response modifiers are in progress.     

Protective role of nitric oxide-mediated inflammatory response against lipid peroxidation in ultraviolet B-irradiated skin

Ultraviolet (UV) irradiation is known to induce serious oxidative damage in the skin via lipid peroxidation. Nitric oxide (NO) synthesized by keratinocytes, melanocytes and endothelial cells in response to proinflammatory cytokines and UV radiation, has been reported to prevent UV-induced apoptosis in the skin. We have examined the effects of NO on UVB-induced lipid peroxidation in murine skin in vivo. UVB induced a dose-dependent increase in lipid peroxidation of skin extracts in vitro; however, lipid peroxidation in the skin in vivo remained unaffected at irradiation doses of less than 1.0 J cm-2 and decreased significantly at doses over 1.5 J cm-2 (P < 0.01). Time-delayed inhibition of lipid peroxidation in the skin in vivo was observed after irradiation at 1.5 J cm-2. Administration of N G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, enhanced lipid peroxidation (P < 0.05), while it suppressed the ear-swelling response (ESR), a biological marker of inflammation. By contrast, administration of sodium nitroprusside, an NO enhancer, suppressed lipid peroxidation (P < 0. 01), while it enhanced the ESR. Expression of inducible nitric oxide synthase (iNOS) was observed from 12 to 48 h postirradiation at doses of 0.4-1.6 J cm-2. The UVB-induced iNOS expression was markedly inhibited by L-NAME, suggesting that iNOS is a major enzyme in the production of NO. These results suggest that NO acts as a mediator of the inflammatory response in UVB-irradiated skin, and that lipid peroxidation is inversely regulated with the NO-mediated inflammatory response in vivo.     

Photosensitivity reactions in black skin

The findings and discussions in this article clearly point out the need for a better understanding not only of the general field of photobiology and photosensitivity reactions but in particular of the role of melanin as well as the genetic bases of these diseases that have not been clearly defined to date. In other words, these discussions clearly demonstrate the need for comprehensive research into the area of photosensitivity in black skin. The fact that black individuals tend to avoid tanning as well as to avoid prolonged exposure to sunlight because of the tremendous heat load that it induces, with consequent discomfort, undoubtedly has played a role in the lower incidence of photosensitivity reactions diagnosed to date. However, this has changed, and the incidence of adverse effects has been increasing in recent years since sunning became fashionable.