Experimental immunology Cytokine signatures of human whole blood for monitoring immunosuppression

Abstract

How to evaluate status of the immune system is extremely critical for clinical immunosuppressive treatment. In this study, we tested the secretion of cytokines in undiluted whole blood samples stimulated with Phorbol 12-myristate 13-acetate (PMA) and ionomycin (IONO), and compared the effects of dexamethasone (DEX), cyclosporine A (CsA) or mycophenolic acid (MPA), either alone or in combination, on cytokine profiles. The results showed that both DEX and CsA dose-dependently inhibited the production of eleven cytokines: interleukin (IL)-2, IL-4, IL-5, IL-6, IL-13, IL-17, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). Unexpectedly, MPA showed no obvious influences except for the mild inhibition on GM-CSF production. In combination treatment, cytokine profiles reflect not only the synergistic effects among drugs, but also the specific effect of the individual drug. Thus, the effects of different immunosuppressants could be reflected through their specific cytokine signatures, which can be applied to maximize immunosuppressive effects, while to minimize risk of infections and help physicians to reasonably apply immunosuppressants.

Establishment of the Reference Intervals of Lymphocyte Function in Healthy Adults Based on IFN-γ Secretion Assay upon Phorbol-12-Myristate-13-Acetate/Ionomycin Stimulation

“…Cytokine monitoring has been proven useful in selection of immunosuppressive therapy, prediction of graft rejection, and progression of various diseases involving immunological abnormalities ( 23 , 24 ). Previous studies have shown that IFN-γ production is a useful biomarker of graft dysfunction, cancer progression, and infectious disease prognosis ( 25 – 27 ).…”

T-lymphocyte in ANCA-associated vasculitis: what do we know? A pathophysiological and therapeutic approach

“…By contrast, other authors did not find evidence of this expanded Th17 response in AAV [20, 21, 34]. It may be hypothesized this is due to a high susceptibility of this cellular subset to steroids, as a possible explanation [35], or due to the variety of cytokines in the IL-17 family. For instance, Krohn et al .…”

Evidence for a More Disrupted Immune-Endocrine Relation and Cortisol Immunologic Influences in the Context of Tuberculosis and Type 2 Diabetes Comorbidity

“…Although TB+DM continued to show a remarkable response despite this steroid treatment. Cortisol inhibitory effects on pro-inflammatory cytokine production are achieved by several transcriptional repression mechanisms (93)(94)(95)(96)(97), with some inconsistencies as to its role in the production of anti-inflammatory mediators in light of evidence reporting a stimulating or inhibitory influences on IL-10 in vitro synthesis (98)(99)(100)(101)(102). Whether the present diminished IL-10 production is to some extent related to the decreased TNF-α and IFN-γ synthesis, which by themselves may promote IL-10 production (103), remains to be established.…”