Astilbin inhibits contact hypersensitivity through negative cytokine regulation distinct from cyclosporin A.
BACKGROUND
IL-10 is known as a negative regulator for inflammatory diseases, including contact dermatitis. However, only a few drug candidates are reported to induce endogenous IL-10.


OBJECTIVE
We sought to elucidate a new mechanism underlying the immunosuppressive properties of astilbin through negative cytokine regulation in comparison with the effective pattern with cyclosporin A.


METHODS
Contact hypersensitivity was induced in mice with picryl chloride. Lymph node cells were isolated for adoptive transfer and cytokine assays.


RESULTS
Astilbin significantly inhibited contact hypersensitivity when given in the elicitation phase but not in the sensitization phase, whereas cyclosporin A inhibited both phases. Lymph node cells from donor mice administered astilbin failed to adoptively transfer the hypersensitivity. Astilbin in vivo remarkably induced IL-10 expression in lymph node cells at an earlier time and decreased TNF-alpha and IFN-gamma expression at a later time. Furthermore, the in vivo neutralization of IL-10 significantly impaired the effect of astilbin on contact hypersensitivity. In the isolated lymphocytes sensitized with picryl chloride in vivo and challenged with trinitrobenzene-sulfonic acid in vitro, astilbin did not affect the cell proliferation but modulated the above cytokine profiles as its in vivo effect in a concentration-dependent manner and furthermore significantly enhanced the expressions of suppressor of cytokine signaling 1 and 3. On the other hand, cyclosporin A strongly inhibited proinflammatory cytokine production but influenced neither IL-10 nor downstream suppressor of cytokine signaling 1 and 3 expression.


CONCLUSIONS
Astilbin alleviates contact hypersensitivity through a unique mechanism involving a negative cytokine regulation through stimulating IL-10, which is distinct from the immunosuppressant cyclosporin A.
Fei
Mingjian
M
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
Wu
Xuefeng
X
Xu
Qiang
Q
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000517:prevention & control*; D005260:Female; D044948:Flavonols / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D012097:Repressor Proteins / Q000235:genetics; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
D002352:Carrier Proteins; D044948:Flavonols; D007166:Immunosuppressive Agents; D012097:Repressor Proteins; C106644:SOCS3 protein, human; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10; C099069:astilbin; D016572:Cyclosporine