Key result
In vitro, tacrolimus strongly inhibited CMV-specific Th1 cytokines (median interferon-γ inhibition 97.5%), whereas mycophenolate preferentially inhibited Th2 cytokines.
Why the study?
Do different immunosuppressive drugs have distinct effects on CMV-specific T-cell cytokine and chemokine responses in vitro?
Do different immunosuppressive drugs have distinct effects on CMV-specific T-cell cytokine and chemokine responses in vitro?
p-value: p=0.004-0.008
Standard and novel immunosuppressive drugs exert distinct, dose-dependent inhibitory effects on CMV-specific T-cell cytokine profiles, which may inform immunosuppression management in patients with CMV replication.
In vitro CMV cytokine effects by drug class merit clinical correlation; leaves open whether they should guide posttransplant immunosuppression.
BACKGROUND: Data on how different immunosuppressive drugs affect cytomegalovirus (CMV)-specific T-cell responses may help guide more rational modification of immunosuppression in patients with CMV replication. We assessed the in vitro effects of individual standard and novel immunosuppressive drugs on a broad range of CMV-specific T-cell responses. METHODS: Peripheral blood mononuclear cells from healthy CMV-seropositive donors were preincubated with serial dilutions of tacrolimus, mycophenolate (MPA), sirolimus, tofacitinib, and belatacept. CMV-pp65 or CMV-pp72 peptide pools were used for stimulation. CMV-specific cytokine (Th1 and Th2) and chemokine responses were determined (a total of 5400 measurements). P<0.01 was set as significant. RESULTS: After CMV stimulation, dose-dependent suppression of Th1, Th2, and chemokines was seen, but significant differences between drugs were present. For example, tacrolimus was more potent in inhibiting CMV-specific Th1 cytokines versus Th2, whereas MPA preferentially inhibited Th2 cytokines. In a comparison of the relative potency of each drug at different dosing ranges, tacrolimus had the strongest Th1 inhibitory effect (median inhibition of interferon-γ at 97.5%; P=0.004-0.008) followed by sirolimus (median inhibition at 82.4%). The remaining agents (MPA, belatacept, and tofacitinib) had less apparent dose-dependent effects on interferon-γ (belatacept median inhibition at 21.5%; P=0.004 vs. tacrolimus). CONCLUSION: Immunosuppression-specific and dose-dependent reductions in CMV-specific cytokine release were observed with significant differences in Th1 versus Th2 profiles and in relative potency of the drugs.
No takes yet. Share an insight, caveat, or question.
Egli et al. (2012) studied Healthy CMV-seropositive donors. Immunosuppressive drugs (tacrolimus, mycophenolate, sirolimus, tofacitinib, belatacept) vs. Other immunosuppressive drugs was evaluated on CMV-specific cytokine (Th1 and Th2) and chemokine responses (p=0.004-0.008). In vitro, tacrolimus strongly inhibited CMV-specific Th1 cytokines (median interferon-γ inhibition 97.5%), whereas mycophenolate preferentially inhibited Th2 cytokines.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: