Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus

• DOI: 10.1007/s10875-012-9679-y
• Publication Date: 2012-03-09T05:01:55Z
• Authors: Rosangela Soares ...; Ana Maria Roselino; Margaret de Castro
• Keywords: Adult; Male; 0301 basic medicine; Binding Sites; Adolescent; Interleukin-6; Tumor Necrosis Factor-alpha; Interleukin-8; Middle Aged; Dexamethasone; Interleukin-10; 3. Good health; Young Adult; 03 medical and health sciences; Receptors, Glucocorticoid; Concanavalin A; Leukocytes, Mononuclear; Humans; Female; Glucocorticoids; Pemphigus; Protein Binding

Glucocorticoids (GC) represent the main treatment for pemphigus; however, some patients show GC resistance. GC sensitivity was evaluated in 19 pemphigus patients and 41 controls by the number of binding sites [B(max) (fmol/mg protein)] and the affinity of GC receptor [Kd (nM)] to dexamethasone (DEX) as well as by the pattern of cytokine by DEX-mediated inhibition of concanavalin-A (Con-A)-stimulated PBMC proliferation. The Kd (15.7 ± 2.8 vs.8.1 ± 1.3) and Bmax (6.5 ± 0.9 vs. 3.9 ± 0.3) were higher in pemphigus than controls (p = 0.002). Considering the values above the 95th percentile of normal group as a cut-off (K(d) > 24.9 nM and B(max) > 8.1 fmol/mg protein), elevated K(d) and B(max) were observed in 9.8% and 2.4% of controls and 15.8% and 36.8% of patients (p = 0.02). PBMC proliferation was stimulated by Con-A and inhibited by DEX (p < 0.001) in both pemphigus and control groups. IL-6 and TNFα (pg/mL) basal production were higher in patients than controls. There was an increment of these cytokines after Con-A stimulation, and they were inhibited by DEX (p = 0.002) in controls and remained elevated in pemphigus (p < 0.02). Patients and controls showed no difference in basal and stimulated production of IL-8 and IL-10. There is an alteration on GC sensitivity in pemphigus patients and a higher production of proinflammatory cytokines. Therefore, in pemphigus patients, proinflammatory cytokines might be involved in the mechanism of GC resistance and/or in its maintenance.