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

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.

• Authors: A Kuhnke, G-R Burmester, S Krauss, F Buttgereit
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 62 Issue 2 Pg. 133-9 (Feb 2003) ISSN: 0003-4967 [Print] England
• PMID: 12525382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• Glucocorticoids
• Concanavalin A

Topics

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