Quantification of immunosuppression by flow cytometric measurement of intracellular cytokine synthesis.
The availability of a method to measure the effects of drugs on immune reactivity should be helpful in optimizing treatment after organ transplantation. Since cyclosporine A (CSA) interferes with activation of T cells and cytokine synthesis, production of IL-2 and IFN-gamma might constitute a marker of this drug's effects. We measured the capacity for mitogen-stimulated production of these cytokines in whole blood by using immunostaining of intracellular and membrane antigens, followed by flow cytometry. The percentage of CD4+ T cells producing IL-2 or IFN-gamma was strongly reduced in 20 transplant patients compared with 24 healthy controls. The capacity for IL-2 production of CD4+ and CD8+ cells correlated inversely with CSA blood levels (P values 0.0087 and 0.0396, respectively). IFN-gamma production by CD4+ T cells showed a negative correlation with the prednisolone dose (P = 0.0175) and, for the CD8+ subset, with CSA trough levels (P = 0.0023). These data show that inhibition of T cell cytokine synthesis by CSA and prednisolone can be quantified.
van den Berg
A P
AP
Department of Gastroenterology and Hepatology, University Hospital, Groningen, The Netherlands. A.P.van.den.Berg@interne.AZG.NL
Twilhaar
W N
WN
van Son
W J
WJ
van der Bij
W
W
Klompmaker
I J
IJ
Slooff
M J
MJ
The
T H
TH
de Leij
L H
LH
D005434:Flow Cytometry; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007371:Interferon-gamma