Bioenergetics of immune cells to assess rheumatic disease activity and efficacy of glucocorticoid treatment

Ann Rheum Dis. 2003 Feb;62(2):133-9. doi: 10.1136/ard.62.2.133.

Abstract

Objective: To investigate whether activity and glucocorticoid treatment of rheumatic diseases are reflected by selected parameters of cellular energy metabolism of peripheral blood mononuclear cells (PBMC).

Methods: PBMC were obtained from 30 healthy volunteers, 28 patients (16 inactive; 12 active) with rheumatoid arthritis, systemic lupus erythematosus, vasculitis, or other autoimmune diseases, and five patients with infectious diseases. Patients with active rheumatic diseases were examined before and 4-5 days after starting, restarting, or increasing the dose of glucocorticoids. Cellular oxygen consumption (as a measure of ATP production), bioenergetic ability to be stimulated, and major ATP consuming processes were measured amperometrically with a Clark electrode.

Results: A normal value for oxygen consumption of 3.84 (SEM 0.1) (all data in nmol O(2)/min/10(7) cells) independent of sex was found. In patients with inactive disease the respiration rate was slightly higher, but was significantly increased in active patients to 4.82 (SEM 0.33) (p<0.001). PBMC from active patients showed a significantly lower bioenergetic response to a mitogenic stimulus than controls (p<0.05). In stimulated cells from active patients there was a significant reduction in cation transport and protein synthesis. All parameters above were almost normalised within 4-5 days upon optimised treatment with glucocorticoids. For comparison, PBMC from patients with active infectious diseases also showed an increased respiration rate; their response to mitogenic stimulation was even higher.

Conclusions: This study shows for the first time that parameters describing the cellular function of PBMC in bioenergetic terms are suitable for (a) describing semiquantitatively the activity of a rheumatic disease and (b) assessing the therapeutic effect on the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Cell Culture Techniques / methods
  • Concanavalin A / immunology
  • Energy Metabolism / drug effects*
  • Energy Metabolism / immunology
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Oxygen Consumption / drug effects
  • Oxygen Consumption / immunology
  • Rheumatic Diseases / blood*
  • Rheumatic Diseases / drug therapy
  • Rheumatic Diseases / immunology
  • Treatment Outcome
  • Virus Diseases / blood
  • Virus Diseases / drug therapy
  • Virus Diseases / immunology

Substances

  • Antirheumatic Agents
  • Glucocorticoids
  • Concanavalin A