Wahle, Matthias and Hanefeld, Gesine and Brunn, Stephan and Straub, Rainer H. and Wagner, Ulf and Krause, Andreas and Haentzschel, Holm and Baerwald, Christoph G. O. (2006) Failure of catecholamines to shift T-cell cytokine responses toward a Th2 profile in patients with rheumatoid arthritis. ARTHRITIS RESEARCH & THERAPY, 8 (5): R138. ISSN 1478-6354,
Full text not available from this repository. (Request a copy)Abstract
To further understand the role of neuro-immunological interactions in the pathogenesis of rheumatoid arthritis (RA), we studied the influence of sympathetic neurotransmitters on cytokine production of T cells in patients with RA. T cells were isolated from peripheral blood of RA patients or healthy donors (HDs), and stimulated via CD3 and CD28. Co-incubation was carried out with epinephrine or norepinephrine in concentrations ranging from 10(-5) M to 10(-11) M. Interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-10 were determined in the culture supernatant with enzyme-linked immunosorbent assay. In addition, IFN-gamma and IL-10 were evaluated with intracellular cytokine staining. Furthermore, basal and agonist-induced cAMP levels and catecholamine-induced apoptosis of T cells were measured. Catecholamines inhibited the synthesis of IFN-gamma, TNF-alpha, and IL-10 at a concentration of 10(-5) M. In addition, IFN-gamma release was suppressed by 10(-7) M epinephrine. Lower catecholamine concentrations exerted no significant effect. A reduced IL-4 production upon co-incubation with 10(-5) M epinephrine was observed in RA patients only. The inhibitory effect of catecholamines on IFN-gamma production was lower in RA patients as compared with HDs. In RA patients, a catecholamine-induced shift toward a Th2 (type 2) polarised cytokine profile was abrogated. Evaluation of intracellular cytokines revealed that CD8-positive T cells were accountable for the impaired catecholaminergic control of IFN-gamma production. The highly significant negative correlation between age and catecholamine effects in HDs was not found in RA patients. Basal and stimulated cAMP levels in T-cell subsets and catecholamine-induced apoptosis did not differ between RA patients and HDs. RA patients demonstrate an impaired inhibitory effect of catecholamines on IFN-gamma production together with a failure to induce a shift of T-cell cytokine responses toward a Th2-like profile. Such an unfavorable situation is a perpetuating factor for inflammation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYSTEMIC-LUPUS-ERYTHEMATOSUS; BLOOD MONONUCLEAR-CELLS; SYMPATHETIC-NERVOUS-SYSTEM; BETA-ADRENERGIC RECEPTORS; PROTEIN-KINASE; MESSENGER-RNA; IFN-GAMMA; BETA(2)-ADRENERGIC RECEPTORS; IMMUNE-RESPONSE; LYMPHOCYTES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Mar 2021 09:08 |
| Last Modified: | 01 Mar 2021 09:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35068 |
Actions (login required)
 |
View Item |
