Etretinate or cyclosporin-A treatment normalizes the enhanced respiratory burst of polymorphonuclear leukocytes in psoriasis

Abstract

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.

The effect of phototherapy on neutrophils

“…Thalidomide, colchicines, and sulfasalazine act by suppressing the production of ROS by neutrophils [36]. Other applications of neutrophil-modulating pharmacologic agents include the use of cyclosporine-A and etretinate to decrease the abnormally elevated respiratory burst of neutrophils seen in patients with psoriasis [37] and the use of hydroxychloroquine to inhibit neutrophil production of superoxide in patients with systemic lupus erythematosus and rheumatoid arthritis [38]. Phototherapy could potentially be used to augment these and other neutrophil-modifying pharmacologic agents; for example, by decreasing required exposure time to drugs with serious adverse effects and potentially providing an alternative maintenance therapy modality.…”

Suppressive Effects of Cyclosporin A and FK-506 on Superoxide Generation in Human Polymorphonuclear Leukocytes Primed by Tumor Necrosis Factor α

“…In contrast to previous studies using peripheral blood PMNL derived from healthy volunteers, several authors have reported the suppressive effects of CsA on O 2 ± generation. Pigatto et al (1988) and Schopf et al (1992) reported that CsA suppressed chemotaxis of PMNL derived from psoriatic patients. On the other hand, in in vivo studies, Tatsuma et al (1994), for example, reported suppression of O 2 ± by CsA in ischemic injury of rat liver and Kubes et al (1991) reported effects of CsA and FK-506 on O 2 ± generation in cat intestine.…”

“…Most authors using PMNL derived from peripheral blood of healthy volunteers have found no effects of these agents on PMNL in in vitro studies. On the other hand, several authors have reported suppressive effects of CsA and FK-506 on O 2 ± generation and chemotaxis of PMNL derived from psoriatic patients (Pigatto et al, 1988;Schopf et al, 1992). In in vivo studies, suppression of O 2 ± formation of PMNL by CsA and FK-506 in ischemic injury of rat liver (Tatsuma et al, 1994) and of cat intestine (Kubes et al, 1991) has been reported.…”

A Highly Decreased Binding of Cyclic Adenosine Monophosphate to Protein Kinase A in Erythrocyte Membranes is Specific for Active Psoriasis

“…Nine patients with psoriasis were treated for 10 wk with a daily dose of 50 mg etretinate, and 21 patients with 2.5±5.0 mg cyclosporine A per kg body weight daily (Sandimmun, Novartis Pharma, Nuremberg, Germany). These patients were enrolled in a treatment study, the details of which have been published before (Schopf et al, 1992). The Institutional Review Board approved this study.…”