Enhanced release of inflammatory mediators from lithium-stimulated neutrophils in psoriasis

Abstract

We have used lithium salts to stimulate degranulation in order to assess neutrophil activity in psoriasis. Evidence is presented for significant enhancement of degranulation of β- glucuronidase (primary granules) and vitamin Bi2-binding protein (secondary granules) from lithium-stimulated neutrophils in psoriatic whole blood. Basal levels of granule markers showed no significant difference between normal and psoriatic neutrophils. On the other hand, enzymes associated with neutrophil function (myeloperoxidase and catalase) were found to be markedly increased in resting psoriatic neutrophils. An important recent development has been the observation that psoriatic neutrophils are ‘activated’ in terms of their neutrophil function. Wahba et al. (1978, 1979) observed enhanced chemotactic and phagocytic properties of isolated psoriatic neutrophils, and Sedgwick, Bergstresser & Hurd (1979, 1980) demonstrated increased adherence of isolated psoriatic neutrophils to glass-wool and nylon fibres. Recently, there have been a number of reports concerning the clearing of psoriasis in patients undergoing haemodialysis and peritoneal dialysis (McEvoy & Kelly, 1976; Buselmeier et al., 1979; Glinski et al., 1979), and it is now believed that improvement was a result of removal of neutrophils rather than some psoriatogenic factor. Lithium salts are commonly used in the treatment of bipolar affective psychosis. Lazarus & Gilgor (1979) drew attention to reports that lithium salts adversely affect the course of psoriasis by direct or indirect mechanisms. They may do so by affecting neutrophil function, thus establishing a relationship between psoriasis and neutrophil activity. Lithium salts can dramatically affect neutrophil activity in terms of granulopoiesis, turnover and migration (Rothstein et al., 1978). We have recently demonstrated that lithium salts have the capacity to induce directly the release of inflammatory mediators from neutrophils in normal whole blood, in the absence of phagocytic stimulation (Bloomfield & Young, 1982). The objective of this investigation was to demonstrate that lithium salts are capable of causing enhanced degranulation from psoriatic neutrophils. In addition, the results would demonstrate in vitro the possible effects which lithium might have in exacerbating psoriasis in vivo, i.e. by causing release of inflammatory mediators from neutrophils which have been shown to be activated.