Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus

Abstract

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 DEXmediated 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 (p00.002). 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 (p00.02). 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 (p00.002) 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.

Autoreactive T cells in the immune pathogenesis of pemphigus vulgaris

“…Similarly, elevated levels of IL‐6 were also found in blister fluids and correlated with disease severity . Serum levels of IL‐6 were also elevated in glucocorticoid‐resistant PV . Serum concentrations of IL‐5, another stimulator of Th2 differentiation, were also elevated in active PV .…”

Prevalence of Metabolic Syndrome and its components in a Brazilian sample of pemphigus patients

“…6 The increased affinity of these receptors for corticosteroids may be associated with good response to the treatment, but also to MetS allied with corticoid side effects.…”

“…3 - 5 Our research group has studied certain aspects of pemphigus pathogenesis which environmental factors allied to genetic predisposition need to be determined. 6 - 10 Treatment consists mainly of systemic corticosteroids, administered orally or by venous pulse therapy, associated, or not, with cyclophosphamide. 11,12 Due to the introduction of rituximab, it is now possible to avoid corticosteroids and minimize their side effects.…”

NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association

“…Variability in glucocorticoid sensitivity can be observed in several conditions, such as chronic inflammatory and autoimmune diseases, including rheumatoid arthritis (12), pemphigus (13), idiopathic nephrotic syndrome (14), dialysis patients (15), and asthma (16). In addition, there is a considerable variability in the sensitivity to glucocorticoids across individuals (17,18) and some of these differences have been related to polymorphisms, some of which relatively frequent in the GR gene (19)(20)(21)(22).…”