Levels of inflammatory cytokines, adrenal steroids, and mRNA for GRα, GRβ and 11βHSD1 in TB pleurisy

Tuberculosis (Edinb). 2013 Nov;93(6):635-41. doi: 10.1016/j.tube.2013.07.008. Epub 2013 Aug 7.

Abstract

Our previous work on the immune-endocrine features of patients with pulmonary tuberculosis (TB) showed markedly decreased plasma levels of dehydroepiandrosterone (DHEA) together with augmented concentrations of Cortisol and pro- and anti-inflammatory cytokines. Studies in peripheral blood mononuclear cells (PBMC) indicated a lower mRNA α/β ratio of glucocorticoid receptors -GR- together with a higher 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) mRNA expression in cases with severe pulmonary TB. Since Pleural TB (PLTB) is a rather benign manifestation of TB, we now analyzed the systemic and local immune-endocrine profile as well as the GRα, GRβ, 11βHSD1 and 11βHSD2 transcripts in PBMC and pleural effusion mononuclear cells (PEMC) of patients with PLTB. PLTB patients had increased levels of IL-1β, IL-6 and IFNγ together with reduced Cortisol and DHEA concentrations in pleural fluids. Also, a significantly increased expression of 11βHSD1 and GRα was found in PEMC compared to PBMC. Findings point out to an appropriate immune response and a substantial inflammatory reaction, wherein the low Cortisol concentrations may be equally effective, because of the increased expression of GRα and 11βHSD1 transcripts which may optimize the immunomodulatory properties of Cortisol.

Keywords: 11βHSD1; Cytokines; Glucocorticoid receptor; Immunoendocrine interaction; Pleural tuberculosis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / biosynthesis
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / biosynthesis
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics
  • Adrenal Cortex Hormones / blood*
  • Adult
  • Aged
  • Cytokines / blood*
  • Female
  • Gene Expression
  • Humans
  • Hydrocortisone / blood
  • Inflammation Mediators / blood*
  • Male
  • Middle Aged
  • Pleural Effusion / immunology
  • Pleural Effusion / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Glucocorticoid / biosynthesis
  • Receptors, Glucocorticoid / genetics
  • Specimen Handling / methods
  • Tuberculosis, Pleural / blood*
  • Tuberculosis, Pleural / immunology

Substances

  • Adrenal Cortex Hormones
  • Cytokines
  • Inflammation Mediators
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • glucocorticoid receptor alpha
  • glucocorticoid receptor beta
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • HSD11B1 protein, human
  • Hydrocortisone