Twenty four patients were studied prior to and after 6 and 12 weeks therapy with isotretinoin (17 patients) for acne and related disorders, or with etretinate (7 patients) for psoriasis and related disorders. Patients treated with isotretinoin had a significant reduction in natural killer cell activity at an effector: target cell ratio of 100: 1 at 12 weeks and also a reduction in natural killer cell numbers at this time. Patients treated with etretinate had elevated natural killer cell activity and a significant elevation of natural killer cell numbers at 12 weeks. Other tests which were performed and showed no significant change at 6 or 12 weeks compared with starting levels included lymphocyte transformation in response to phytohaemagglutinin, pokeweed mitogen and concanavalin A, total numbers of circulating T lymphocytes, B lymphocytes and T helper and T suppressor subsets, numbers of epidermal Langerhans cells and serum levels of IgA, IgM and IgE. In view of the involvement of natural killer cells in the initial phase of organ rejection, these results suggest that isotretinoin is the safer of the two retinoids if administration to renal transplant recipients is considered, particularly in the immediate post-transplant period.
Summary It is well‐recognized that patients with atopic dermatitis handle certain cutaneous viral infections poorly. As natural killer (NK) cell activity is considered to contribute to the immune response to viral infection, seven young adults with atopic dermatitis had their NK cell function assessed over a 12‐month period. Natural killer cell activity was found to correlate inversely with disease activity. The more active the disease, the greater was the reduction in NK cell function (P<0.01). In addition, a strong correlation between clinical activity and IgE was shown (P<0.001).
Summary Natural‐killer (NK)‐cell activity was measured in the peripheral blood of twenty patients with atopic dermatitis and in a group of thirteen age‐matched non‐atopic controls (nine subjects on thirteen occasions). The method uses a chromium‐release assay with the human leukaemia cell line, K562, labelled with 5lCr as the target cell. A highly significant reduction in NK‐cell activity was found in the patients with atopic dermatitis.
A 33-year-old female with cyclical neutropenia and a reciprocally cycling T8 (suppressor/cytotoxic) lymphocytosis was investigated. T8 lymphocytes ranged between 1.4 and 5.6 X 10(9)/l and a significant proportion (50-75%) were preactivated (1a+). Fc gamma receptors were detected in only a minority (7-10%). Functional studies on the lymphocytes indicated that despite their phenotype, little natural killer and reduced suppressor activities were present. Anti-granulocyte antibodies were not detectable in the serum. Production of colony stimulating activity (CSA) was assessed in the patient and control subjects' lymphocytes. Using a methylcellulose marrow culture system, the CSA production by the patient's lymphocytes was markedly increased compared with the control. Monoclonal antibody cytotoxic experiments confirmed that the T8 lymphocytes were responsible. As peaks of circulating T8 lymphocytes were synchronous with granulopoietic activity in the marrow, the above findings may represent a homeostatic mechanism which is attempting to compensate for an underlying stem cell defect.
Peripheral blood natural killer (NK) cell activity of a group of 10 healthy non-atopic volunteers was reduced following the topical application of 15 g of 0.1% betamethasone valerate ointment to the skin nightly for 1 week. In contrast, no such effect was observed when the inactive base of the steroid ointment was used. NK cell activity dropped significantly by day 7 (P less than 0.05) and then recovered, although NK cell activity at day 22 was still lower than that observed at the start of the experiment. These findings suggest that topically applied steroid is absorbed in sufficient amounts to cause a systemic effect on NK cell function. This may have implications in a number of dermatological disorders, including atopic dermatitis, where topical steroids form the mainstay of treatment.
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