Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus

Author(s)

Chriguer, Rosangela Soares ^[1] ; Roselino, Ana Maria ^[1] ; de Castro, Margaret ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Internal Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF CLINICAL IMMUNOLOGY; v. 32, n. 4, p. 786-793, AUG 2012.
• Web of Science Citations: 12

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 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 TNF alpha (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. (AU)

• FAPESP's process: 03/09857-0 - Neuroendocrine mechanisms of the regulation of the hypothalamic-pituitary-adrenal axis in clinical and experimental models of resistance to glycocorticoids and sepsis
• Grantee: Ayrton Custodio Moreira
• Support Opportunities: PRONEX Research - Thematic Grants