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Ethanol has been reported to exacerbate psoriasis. Since immunological mechanisms are considered to be important for the pathogenesis of psoriasis, we compared the effects of ethanol on lymphocyte proliferation in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin in (PHA)-induced uptake of 3H-TdR to measure lymphocyte proliferation. Ethanol was added to cultures at concentrations ranging from 0.5 to 0.0005% (vol./vol.). We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (P < 0.002). Spontaneous blastogenesis in both controls and patients remained stable under ethanol. In controls, ethanol suppressed the PHA-driven lymphocyte proliferation in a dose-dependent fashion. By contrast, in patients with psoriasis ethanol significantly increased lymphocyte proliferation by 2-3 times (p < 0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally enhanced by minimal doses of ethanol.

The purpose of this study was to measure soluble CD14 (sCD14) molecules in the skin and in serum of patients with psoriasis. CD14 is a newly discovered cell surface marker on monocytes that is shed after cell activation. The following procedures were used: suction blisters were raised over the abdominal skin of 9 healthy control individuals and 8 patients with psoriasis. Serum of 17 healthy controls and 17 patients with psoriasis was collected. sCD14 was determined in suction blister fluid and serum by the ELISA technique. The clinical status of psoriasis was rated by the psoriasis area and severity index (PASI score). We found that sCD14 levels in suction blisters of healthy skin (1,050 +/- 236 ng/ml, mean +/- SE) were similar to those of nonlesional psoriatic skin (841 +/- 113 ng/ml). By contrast, control serum contained 2,687 +/- 167 ng/ml, but psoriatic serum 4,059 +/- 388 ng/ml sCD14 (p = 0.001, Wilcoxon test). Linear-regression analysis revealed that serum sCD14 levels and the PASI score of patients did not correlate. We conclude that there is an abnormal monocyte stimulation in blood but not in nonlesional skin in psoriasis that is independent from the clinical status expressed by the PASI score.

Fibrin deposition is an important histopathological feature of inflammatory skin lesions and is mediated in part, by procoagulants generated by mononuclear leucocytes (MNL). We examined whether MNL from patients with atopic dermatitis or psoriasis generate enhanced procoagulant activity (PCA). MNL isolated from the peripheral blood of 15 healthy control individuals, 15 patients with atopic dermatitis and 15 patients with psoriasis were incubated for 24 h in the presence or absence of bacterial lipopolysaccharide (LPS). MNL or the cell culture supernatants were then added to recalcified human plasma to determine the clotting time. We found that in both atopic dermatitis and psoriasis MNL cultured in the presence or absence of LPS expressed greatly enhanced PCA (p < 0.01 to < 0.002). Supernatants from MNL cultures from patients with psoriasis, but not those from patients with atopic dermatitis, also generated augmented PCA (p < 0.002). In psoriasis, PCA normalized after successful topical treatment with anthralin. We conclude that enhanced PCA is a characteristic feature of MNL in both atopic dermatitis and psoriasis. In psoriasis the enhanced PCA is directly related to disease activity.

A newly developed ELISA was used to detect and quantify the presence of a soluble form of intercellular adhesion molecule-1 (sICAM-1) in the circulation of healthy individuals compared with patients with psoriasis vulgaris. Seventeen psoriatic patients were studied. The extent of skin lesions was rated by the psoriasis area and severity index (PASI). Seventeen age- and sex-matched healthy individuals served as controls. Serum levels were measured by an ELISA technique utilizing an anti-ICAM-1 murine monoclonal antibody bound to the solid phase, and a second, peroxidase-conjugated monoclonal antibody reacting with sICAM-1. Serum levels in controls were 358.8 +/- 87.9 ng/ml sICAM-1, and 480.5 +/- 133.6 ng/ml in psoriatics (mean +/- SD; P = 0.02). In psoriasis, sICAM-1 levels were found to be directly proportional to the PASI score (y = 363.002 + 8.525x, R = 0.55, P = 0.021). These data suggest that the concentration of sICAM-1 in serum increases during psoriatic inflammation. The origin and function of sICAM-1 in psoriasis remain to be defined.

Chloroquine is known to exacerbate psoriasis. Since immunological stimuli are considered to be important for the pathogenesis of psoriasis, we compared the effects of chloroquine on cell-mediated immunity in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin (PHA)-induced uptake of 3H-thymidine to measure lymphocyte proliferation. Chloroquine was added to the cultures at concentrations ranging from 0.022 to 220 microM. We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (p < 0.002). The spontaneous blastogenesis in both controls and patients remained stable under chloroquine. In PHA-driven cultures in controls, 0.022-2.2 microM chloroquine had no effect, higher concentrations of the drug suppressed proliferation. In patients, 22 microM chloroquine surmounted the suppression of the PHA-induced proliferative response found in controls; moreover, 2.2-0.022 microM chloroquine increased lymphocyte proliferation by > 300% (p < 0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally stimulated by the addition of pharmacological doses of chloroquine.

During a therapeutic trial to treat psoriasis with either etretinate or cyclosporin A (CyA) we measured the respiratory burst activity of polymorphonuclear leukocytes (PMN). Six patients received 0.5-0.75 mg/kg etretinate and 14 patients 2.5-5.0 mg/kg CyA over a period of 10 weeks. The extent of psoriasis was graded by the psoriasis area-and-severity index (PASI score). The respiratory burst of PMN isolated from the peripheral blood was measured employing luminol-enhanced chemiluminescence at weeks 0, 3 and 10 and compared with that of 26 healthy control individuals. PMN were stimulated with zymosan particles, aggregated immunoglobulin (aggIg) and concanavalin A (ConA). Both treatment regimens improved psoriasis; at 10 weeks there was an approximate 40% PASI score reduction under etretinate and an 80% improvement under CyA. Before treatment the respiratory burst was abnormally high under stimulation with the three stimuli in patients (p = 0.021 to less than 0.0001). After 3 to 10 weeks PMN activity normalized in all patients and even tended to drop below values correlating with an improvement in skin lesions. We conclude that the elevated respiratory burst of PMN in psoriasis normalizes under treatment with both etretinate and CyA.

Although a number of skin diseases are characterized by the presence of an increased number of phagocytes in their lesions, the effects of alcohol on phagocytic functions are not clearly understood. Therefore, we measured the influence of ethanol and acetaldehyde on the generation of oxygen radicals, chemotaxis and the release of lysosomal enzymes from human phagocytes. We added 0.03%-3% ethanol and 0.005%-0.25% acetaldehyde to cell cultures. We found that both ethanol and acetaldehyde suppressed the generation of oxygen radicals from granulocytes and monocytes; the ID50 was achieved at concentrations of approximately 0.25% for ethanol and 0.03% for acetaldehyde. A significant inhibition of granulocyte chemotaxis was first noted with 0.063% ethanol and 0.016% acetaldehyde. Ethanol and acetaldehyde inhibited the release of the lysozyme of monocytes at concentrations of greater than 0.75% and greater than 0.03% respectively, but granulocytes were unaffected; the release of beta-glucuronidase and lactate dehydrogenase remained stable. Due to the high volatility of the agents, especially acetaldehyde, under the experimental procedures employed, the actual concentrations of the agents were probably lower and similar to those measured in vivo. Our results indicate that defined phagocytic functions are strongly inhibited by concentrations of ethanol and acetaldehyde which are associated with moderate to severe inebriation.

The aim of the study was to determine a biochemical basis for the augmented oxidative metabolism found in mononuclear leukocytes (MNL) of patients with active psoriasis. Dehydroepiandrosterone (DHEA) is known to inhibit glucose-6-phosphate dehydrogenase (G-6-PDH). We determined the activity of G-6-PDH as well as the penetration and metabolism of DHEA - diminished plasma concentrations of which have been found in psoriatics previously - in 16 patients with active psoriasis and 16 controls. MNL in patients with psoriasis possessed 52% more (p less than 0.05) G-6-PDH activity, based on cell number, and 34% more (p less than 0.05) activity, based on soluble protein. No difference in DHEA penetration and metabolism in MNL was found between psoriatics and controls, in contrast with previous findings of reduced penetration and increased reduction in erythrocytes of psoriatics. We conclude that the enhanced G-6-PDH activity in MNL of patients with active psoriasis is not due to altered DHEA penetration or metabolism.

Human melanomas were investigated for the presence of high-affinity estrogen-, gestagen-, and glucocorticoid-binding proteins. A statistically significant difference was found for mean estrogen receptor (ER) concentrations in melanomas of male versus female origin: female origin 37.6 (0-107) fmol/mg protein, male origin 3.9 (0-8.3) fmol/mg protein. No significant difference between sexes was found for gestragen receptors: 41.5 (0-194) fmol/mg protein for melanomas of female origin versus 99 (0-362) fmol/mg protein for male. Sucrose density gradient analyses revealed specific binding for both receptor types in the 4-5 S region as well as in the 8 S region. The binding affinities were in the same order of magnitude as reported for receptors found in typical steroid target organs. No significant difference in receptor values depending on sex was found for the glucocorticoid receptor: 19.2 (0-43) fmol/mg protein.

We examined granulocytes or polymorphonuclear leukocytes (PMN) in an HLA B8+ patient with palmoplantar pustulosis (PPP). Controls included another patient with PPP, however, lacking this antigen and a healthy, HLA B8+ person. Chemiluminescence (CL) served to monitor the respiratory burst in PMN comparing as stimuli zymosan, opsonized zymosan, phorbol myristate acetate, as well as aggregated immunoglobulin (aggIg), the latter as Fc-receptor (FcR) stimulus. FcR density on PMN was determined using 125I-IgG and expressed in the form of Scatchard plots. The effects of serum on the aggIg-induced CL were also measured. We found both control individuals to respond to stimulation by aggIg as a function of a dose-dependent increase of CL. By contrast, the HLA B8+ patient with PPP failed to respond to aggIg; only the highest concentration of aggIg induced marginal CL. Conversely, stimulation by the other agents was similar in all three individuals. The patient with the functional FcR defect expressed 2.5 times more FcR/PMN than the controls. No difference emerged in comparing autologous serum with a reference normal serum on the aggIg-induced CL, ruling out saturation by serum factors alone to be a cause for the defect. In remission, the functional FcR was absent. Our results suggest a defect of signal transduction in PMN from numerically enhanced FcR to the cytosol in the patient with PPP.

Based on recent findings indicating suppression of lymphocytic functions by seminal plasma (SP) we tested the effects of SP from men with normo- and oligozoospermia (n = 7, each) on the generation of luminol-enhanced chemiluminescence (CL) of polymorphonuclear leukocytes (PMN) and monocytes (M psi) stimulated in vitro with zymosan. We found a complete suppression of CL of PMN and M psi by undiluted SP's, 1,000-fold dilutions still induced greater than or equal to 20 percent inhibition. There was no difference between normo- and oligozoospermic men in inhibition of CL both with PMN and M psi. Protein concentrations of SP's were closely the same; all SP were free of the complement components C4 and C3c. After dialysis of SP the inhibition of PMN - and M psi - generated CL was no longer present. Our results demonstrate that SP exerts extremely potent inhibition of cells mediating nonspecific defense and/or antigen presentation. The inhibitor appears to be of low molecular weight. These findings may be important for infections acquired by the genital tract and may provide an explanation for the immunotolerance of spermatozoa in the female reproductive system.

Absorption and clinical efficacy of a preparation containing 20% benzoyl peroxide were studied in 20 patients with leg ulcers of varying etiology. Benzoic acid formed from benzoyl peroxide on penetration through the skin cannot be demonstrated in the plasma until three days after commencing application at the earliest. This indicates a building up of deposits of benzoyl peroxide in the skin. The plasma benzoic acid levels in all patients amounted to less than 5 mumol/l and is therefore toxicologically inoffensive. Clinically, the known therapeutic effects of benzoyl peroxide were confirmed. Neither sensitization nor allergic reactions were found in the 20 patients taking part in this study.

Based on reports suggesting aberrant cell-mediated immunity and altered infiltration of immunocompetent cells into the skin in psoriasis, we studied the stimulation of T cells by autologous non-T mononuclear leukocytes (autologous mixed lymphocyte reaction, AMLR) and by epidermal cells isolated from lesional and clinically uninvolved skin in psoriasis (autologous mixed epidermal cell lymphocyte reaction, AMECLR). Age- and sex-matched individuals served as controls. We found that the AMLR in psoriasis (n = 11) was similar to that in healthy controls (n = 16); furthermore, cell proliferation was alike in the presence of either 5% AB-serum or autologous serum. By contrast, while the AMECLR in healthy controls (n = 9) resembled that in psoriatics employing epidermal cells from univolved skin, epidermal cells from lesional sites (n = 10) induced a significantly higher proliferation of autologous T cells in the AMECLR (P less than 0.01). We conclude that the in vitro stimulation of T cells by non-T mononuclear leukocytes is normal in psoriasis and is not regulated by autologous serum. Lesional psoriatic epidermal cells, however, are more active in stimulating autologous T cell proliferation than cells from univolved psoriatic or normal epidermis.