Serum cytokine analysis in a positive chemoprevention trial: selenium, interleukin-2, and an association with squamous preneoplastic disease.
This study represents a multiplex cytokine analysis of serum from a 10-month randomized, controlled trial of 238 subjects that investigated the effects of selenomethionine and/or celecoxib in subjects with mild or moderate esophageal squamous dysplasia. The original chemoprevention study found that, among those with mild dysplasia, selenomethionine treatment favorably altered dysplasia grade. The current analysis found that selenomethionine downregulated interleukin (IL)-2 by 9% (P = 0.04), whereas celecoxib downregulated IL-7 by 11% (P = 0.006) and upregulated IL-13 by 17% (P = 0.008). In addition, an increase in IL-7 tertile from baseline to t10 was significantly associated with an increase in dysplasia grade, both overall [odds ratio (OR), 1.47; P = 0.03] and among those with mild dysplasia at t0 (OR, 2.53; P = 0.001). An increase in IL-2 tertile from baseline to t10 was also nonsignificantly associated with worsening dysplasia for all participants (OR, 1.32; P = 0.098) and significantly associated with worsening dysplasia among those with mild dysplasia at baseline (OR, 2.0; P = 0.01). The association of increased IL-2 with worsening dysplasia remained significant in those on selenomethionine treatment who began the trial with mild dysplasia (OR, 2.52; P = 0.03). The current study shows that selenomethionine supplementation decreased serum IL-2 levels, whereas celecoxib treatment decreased IL-7 levels and increased IL-13 levels during a 10-month randomized chemoprevention trial. An increase in IL-2 or IL-7 was associated with increased severity of dysplasia over the course of the trial, especially in those who began the trial with mild dysplasia. The favorable effect of selenomethionine on esophageal dysplasia in the original trial may have been mediated in part by its effect in reducing the levels of IL-2.
Roth
Mark J
MJ
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7232, USA. mr166i@nih.gov
Katki
Hormuzd A
HA
Wei
Wen-Qiang
WQ
Qiao
You-Lin
YL
Bagni
Rachel
R
Wang
Guo-Qing
GQ
Whitby
Denise
D
Dong
Zhi-Wei
ZW
Gail
Mitchell H
MH
Limburg
Paul J
PJ
Giffen
Carol A
CA
Taylor
Philip R
PR
Dawsey
Sanford M
SM
D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068579:Celecoxib; D016207:Cytokines / Q000097:blood*; D004938:Esophageal Neoplasms / Q000097:blood* / Q000517:prevention & control; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000097:blood* / Q000517:prevention & control; D016017:Odds Ratio; D011230:Precancerous Conditions / Q000097:blood* / Q000188:drug therapy; D011720:Pyrazoles / Q000627:therapeutic use; D012645:Selenomethionine / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use
D016588:Anticarcinogenic Agents; D016207:Cytokines; D007376:Interleukin-2; D011720:Pyrazoles; D013449:Sulfonamides; D012645:Selenomethionine; D000068579:Celecoxib