IMPAIRMENT OF THE INHIBITORY EFFECT OF SODIUM ON BASOPHIL HISTAMINE-RELEASE IN PATIENTS WITH SYSTEMIC-SCLEROSIS

It has been demonstrated that Na+ down-regulates IgE-dependent and IgE -independent histamine release from basophils of normal subjects. The aim of this study was to evaluate whether Na+ exerts its inhibitory ef fect on basophil histamine release in patients with systemic sclerosis (SSc). Peripheral blood leucocytes were stimulated with anti-IgE, N-f ormyl-methionyl-leucyl-phenylalanine (fMLP) and IL-3 in the presence o f high and low Na+ concentrations, and histamine release was measured by a fluorometric method. The dose-response curves of histamine releas e induced by the above stimuli were similar in SSc patients (n = 15) a nd in normal subjects (n = 39). Na+ removal from the extracellular med ium and its isosmotic replacement with choline chloride led to a signi ficant increase of anti-IgE- and fMLP-induced histamine release in nor mal subjects, but not in SSc patients. In the former population, hista mine release induced by an optimal dose of anti-IgE (1/5000) was 26.4/-3.1% in high Na+ and 59.3+/-3.5% in low Na+ (mean+/-s.e.m., P < 0.00 01), whereas in the latter population mean histamine release was 20.4/-5.1% in high Na+ and 15.8+/-2.9% in low Na+ (P NS). A similar trend was observed when basophils were stimulated with fMLP. Na+ exerted a d ose-dependent inhibitory effect on anti-IgE- and fMLP-induced histamin e release in normal subjects, but not in SSc patients. IL-3-induced hi stamine release from basophils of SSc patients was increased in a low- Na+ solution, but to a lesser. extent when compared with normal contro ls. Therefore basophils from normal subjects and SSc patients behave i n a different way when stimulated in a low-Na+ medium. The inhibitory effect of Na+ on basophil histamine release is impaired in SSc patient s, and this abnormality could contribute to basophil dysfunction.