Clinical relevance of curcumin-induced immunosuppression in living-related donor renal transplant: an in vitro analysis.
OBJECTIVE
In this study, we assessed the immunosuppressive potential of curcumin, a pharmacologically safe and cost-effective naturally occurring polyphenolic phytochemical, on the induction of Th1 cytokines that are frequently overexpressed in patients experiencing rejection after renal transplant.


METHODS
Peripheral blood lymphocytes obtained from 68 renal transplant recipients and 17 healthy controls were treated with curcumin before stimulation with phorbol myristate acetate and were analyzed with flow cytometry for interferon-alpha and interleukin 4 positive cells.


RESULTS
Patients experiencing acute rejection exhibited a high level of interferon-alpha (38.3% +/- 11.2%) and a low level of interleukin 4 (4.2% +/- 2.0%) in their activated peripheral blood lymphocytes. The use of curcumin dose-dependently decreased interferon-alpha induction in cultures from healthy controls (28.1% +/- 4.8%-10.7% +/- 5.3%, P < .001), patients experiencing acute rejection (38.3%-18.3%, P < .001), and those experiencing chronic rejection (40.6%-12.9%, P = .01) when compared with corresponding untreated cultures. In contrast, curcumin exerted only a marginal effect on interleukin 4 expression. Interestingly, curcumin was found to inhibit nuclear factor kappa beta activation by blocking the degradation of the inhibitory unit I kappa B alpha. We also noted the synergistic inhibitory effect of in vitro treatment with curcumin in combination with cyclosporine on the peripheral blood lymphocytes of patients experiencing acute rejection.


CONCLUSIONS
These data provide a rationale for the use of curcumin as an affordable, pharmacologically safe, adjuvant immunosuppressant when used with cyclosporine and suggest that curcumin can effectively suppress Th1 cytokine induction after renal transplant.
Bharti
Alok C
AC
Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
Panigrahi
Arundhati
A
Sharma
Prabhat K
PK
Gupta
Nivedita
N
Kumar
Rakesh
R
Shukla
Shirish
S
Bhowmik
Dipankar M
DM
Agarwal
Sanjay K
SK
Guleria
Sandeep
S
Mehra
Narinder K
NK
D000208:Acute Disease; D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007194:India; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016030:Kidney Transplantation / Q000009:adverse effects; D019520:Living Donors; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D055815:Young Adult
C508598:IL4 protein, human; D007166:Immunosuppressive Agents; D008934:Mitogens; D016328:NF-kappa B; D015847:Interleukin-4; D007371:Interferon-gamma; D016572:Cyclosporine; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate