J. Knop

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis

Background SDZ ASM 981 is a selective inhibitor of the production of pro‐inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases.

Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus

The therapeutic effect of thalidomide in chronic discoid lupus erythematosus (CDLE) was studied in sixty patients who were followed up for 2 years. In fifty‐four patients (90%) a complete or marked regression of the disease was observed, but when the thalidomide was stopped, thirty out of forty‐one (71%) patients relapsed. Patients undergoing a second course of thalidomide treatment again responded well. Nine of the patients in whom the disease recurred after successful treatment with thalidomide and who had been unresponsive to intermittent treatment with antimalarials, showed a good response to a second or third course with thalidomide. Mild side‐effects were common and 25% of patients complained of slight to moderate polyneuritic symptoms. Since electroneurological examinations had not been performed before the thalidomide therapy, the frequency of neurological side‐effects cannot be accurately calculated but we recommend neurological examinations before and periodically during thalidomide treatment.

Treatment of chronic discoid lupus erythematosus with thalidomide

SummaryIn an uncontrolled study the therapeutic effect of thalidomide on chronic discoid lupus erythematosus was investigated. In 24 patients (17 women, 7 men) with a history ranging from 0.5–32 years and unresponsive to any previous therapeutic measures, complete or substantial regression of the disease was observed in 19 cases (80%) after treatment with thalidomide. Side effects were somnolence, constipation, exanthema, oral dryness, and circulatory disturbances. None of these effects were serious.ZusammenfassungIn einer unkontrollierten Studie wurde die therapeutische Wirksamkeit von Thalidomid beim chronisch discoiden Lupus erythematosus untersucht. Die Studie umfaßte 24 Patienten (17 Frauen, 7 Männer), die seit 0.5–32 Jahren an der Erkrankung litten und deren Hauterscheinung durch jegliche, bisher durchgeführten Behandlungen unbeeinflußt geblieben waren. Neunzehn Patienten (80%) zeigten eine vollständige oder erhebliche Rückbildung der Herde unter Thalidomidgabe. Als Nebenwirkungen traten Müdigkeit, Obstipation, Exanthem, Mundtrockenheit und Kreislaufprobleme auf. Keine dieser Nebenwirkungen waren ernsthafter Natur.

Ultrastructural cytochemical visualization of chromium in the skin of sensitized guinea pigs

SummaryUsing a modified sulfide silver method for electron microscopy, the intraepidermal and intracellular localization of epicutaneously applied potassium dichromate was investigated at varying times in sensitized and nonsensitized guinea pigs. The hapten penetrated rapidly into the epidermis. There was a homogeneous extra-and intracellular staining of the keratinocytes in the upper epidermis. The basal and suprabasal cells, by contrast, exhibited a predominant extracellular and plasma membrane localization of the silver grains. This membrane staining pattern was also observed in the Langerhans cells showing cellular and endocytotic activation in the sensitized animals. No specific cellular uptake of the hapten by the Langerhans cells was found. These results demonstrate that the epicutaneous application of chromate resulted in a characteristic intraepidermal distribution which may be related to the epidermal conversion of the hexavalent chromate to the immunogenic trivalent form. Moreover, the absent intracellular localization of the hapten in the activated Langerhans cells supports the notion that contact allergens can be presented to T cells without prior intracellular processing.

Chemotactic efficiency of various chemoattractants for polymorphonuclear leukocytes in inflammatory acne vulgaris

SummaryThe chemoattractant efficiencies of a Propionibacterium acnes (P. acnes) cell wall preparation, a P. acnes culture supernatant, and a soluble comedonal extract in the presence and absence of autologous serum for polymorphonuclear leukocytes (PMNs) have been compared in the present study. It has been found that all three preparations have no or very little chemotactic activity for PMNs in the absence of serum. In the presence of autologous serum chemotactic factors is generated by all preparations via the alternative complement pathway. The relative efficiencies of the various preparations to induce chemotactic factor by the alternate complement pathway has been evaluated. Based on the bacterial numbers of the original preparations from which the test preparations had been derived the comedonal extract appears to be more efficient in generating chemotactic factor than the other preparations. It is concluded that in vivo generation of chemotactic factors occurs mainly via the alternate complement pathway activated by soluble comedonal factors diffusing through the follicular wall.

Suppression of the elicitation phase of contact allergy by epicutaneous application of alpha-l-fucose

SummaryLocal application of alpha-l-fucose on the ear before elicitation of contact allergy to dinitrofluorobenzene (DNFB) in BALB/c mice results in a suppression of the contact allergic response. However, local application of alpha-l-fucose at the sensitization site on the abdominal wall before sensitizing the animals with DNFB had no inhibitory effect on contact allergy. Alpha-l-fucose has been demonstrated to inhibit lymphokine activity in vitro and manifestation of cellular immunity in vivo. Our results suggest that alpha-l-fucose suppresses contact allergy by locally inhibiting the efferent phase of the cellular immune response.

Leukapheresis in the treatment of cutaneous T-cell lymphomas

In six patients with cutaneous T‐cell lymphomas (CTCL), the effect of leukapheresis (LPH) on the disease and on various immunological and haematological parameters was investigated. Enriched mononuclear cells were removed by continuous centrifugation leukapheresis from the peripheral blood of the patients. A profound and longlasting effect was seen in one patient with the Sézary variant; a moderate response was seen in two other Sézary patients. No benefit was observed in two patients with more aggressive leukaemic disease, and one patient with plaque stage MF responded on two occasions. No limiting side effects were recognized and no consistent changes of immunological or haematological parameters were observed after LPH.

Effect of Corynebacterium parvum-mediated inhibition of lymphocyte proliferation on the effector-and suppressor-lymphocyte response in contact allergy

SummaryThe generation and/or expression of suppressor T lymphocytes (Ts) in contact allergy to 2,4-dinitrofluorobenzene (DNFB) is inhibited by treatment of BALB/c mice with C. parvum. It has been described that C. parvum injected intravenously (IV) or intraperitoneally (IP) suppresses lymphocytic responses via activated macrophages. In this investigation we compared Ts and T-effector lymphocytes of delayed hypersensitivity (TDH) inhibition and suppression of mitogen-induced spleen lymphocyte proliferation by C. parvum to find some correlation between these effects of C. parvum. Various times after IP injection of C. parvum BALB/c mice were tolerized (a) by an epicutaneous antigen overload, (b) by 2,4-dinitrobenzene (DNBSO3 IV, (c) by injection of Ts cells from tolerant donors, or (d) sensitized with an optimal dose (15 μl) of DNFB.Suppressor and effector cell generation and/or function was assessed by sensitization (2×0.5% DNFB) and challenge at the right ear or by transfer of spleen cells from the C. parvum-treated or-untreated tolerized donor to the C. parvum-treated or-untreated recipient, followed by sensitization and challenge of the recipient. From the same pool of C. parvum-treated or-untreated animals, spleens were obtained, weights determined, spleen cells prepared, and mitogen (phythemagglutinin or concanavalin A)-induced lymphocyte proliferation measured.The results show that C. parvum-mediated inhibition of Ts generation in the donor mice correlated — although not entirely — with suppression of mitogen-induced lymphocyte proliferation. Inhibition of Ts function in the recipient by C. parvum did not correlate with suppression of spleen lymphocyte proliferation, i.e., Ts function was inhibited up to 1 week only. Lymphocyte proliferation, however, was inhibited up to 3 weeks after C. Parvum injection. Sensitization of mice was inhibited by C. parvum shortly after injection; 1 week after C. parvum injection, no inhibition of contact sensitivity was observed. These results suggest that Ts-cell generation might be suppressed by a similar mechanism as described for suppression of lymphocyte proliferation, i.e., via suppressive factors released from C. parvum-activated macrophages, however, Ts-cell function appears not to be inhibited by this mechanism. T-effector cells of delayed hypersensitivity are very little affected by C. parvum-mediated suppression.