Evaluating the effects of immunosuppressants on human immunity using cytokine profiles of whole blood.
It is critical to determine the status of the immune system in transplant recipients, but there are currently no clinical methods available to do so. To address this, we have developed an innovative method to evaluate the effects of immunosuppressants that involves measuring phytohemagglutinin (PHA)-stimulated cytokine secretions in vitro in response to treatments with dexamethasone (DEX), FK506 or mycophenolic acid (MPA). The results revealed that DEX nonspecifically and dose-dependently inhibited the production of 12 cytokines (IL-2, IFN-gamma, TNF-alpha, IL-8, IL-1beta, IL-17, IL-4, IL-5, IL-6, IL-10, IL-13, and G-CSF). In contrast, FK506 and MPA selectively inhibited the secretion of IL-2 and IL-13, and MPA unexpectedly increased the production of IL-1beta. Therefore, different immunosuppressants have distinct cytokine signatures that can be used to determine whether there is under- or over-immunosuppression in transplant recipients. Immunosuppressants could be adjusted according to the cytokine profiles to maximize immunosuppressive effects while minimizing the risk of infection.
Liu
Zhanguo
Z
Institute of Transplant Immunology, Organ Transplant Department, Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou 510282, China.
Yuan
Xiaopeng
X
Luo
Yuwei
Y
He
Yi
Y
Jiang
Yong
Y
Chen
Zhonghua Klauz
ZK
Sun
Erwei
E
D001769:Blood / Q000187:drug effects / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007118:Immunoassay / Q000379:methods; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D009173:Mycophenolic Acid / Q000494:pharmacology*; D016377:Organ Transplantation; D010835:Phytohemagglutinins / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D014180:Transplantation
D016207:Cytokines; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D003208:Concanavalin A; D003907:Dexamethasone; D009173:Mycophenolic Acid; D016559:Tacrolimus