[The effects of interleukin-11 on high-dose methotrexate (HDMTX) induced mucositis in Wistar rats].
OBJECTIVE
To explore the therapeutic effect of interleukin-11 (IL-11) on high-dose methotrexate (HDMTX) induced mucositis in Wistar's rats, the proliferative effect on CEM leukemia cell line and the antitumor effect on HDMTX.


METHODS
Ninety-five 5-week old, 120 - 150 grams weight Wistar rats were randomly divided into five groups. Group A is normal control (n = 15), group B MTX control (n = 20), group C IL-11 pretreatment group before MTX injection (n = 20), group D (n = 20) the high dose IL-11 group (475 microg.kg(-1).d(-1)) after MTX injection, group E (n = 20) the low dose IL-11 group (150 microg.kg(-1).d(-1)) after MTX injection. All rats in group B approximately E were given 1 ml MTX intraperitoneally (100 mg/kg). Rats were killed at day 1, 3, 5, 7 after MTX injection. The mortality rates, changes of small intestine tissue morphology and ultra structure were observed. The proliferation of small intestine crypt cell was assayed by proliferating cell nuclear antigen (PCNA) immunohistochemical staining. MTT method was used to detect the proliferation of CEM cell line.


RESULTS
IL-11 treatment resulted in a significant increase of survival of HDMTX treated rats, increased of small intestinal villus length and villus/crypt ratio. IL-11 administration was associated with enhancement of small intestine mucosa recovery after HDMTX therapy. Group C showed a greater effect than group B (P < 0.01). IL-11 had no effect on CEM cell proliferation.


CONCLUSIONS
IL-11 has a significant mitigating effect on high-dose MTX induced intestinal mucositis in rat, and significantly increase the survival of the rats. IL-11 could be safely used in the HDMTX treatment of childhood acute lymphocyte leukemia.
Han
Yue-qin
YQ
Shandong Provincial Hospital, Shandong University, Jinan 252000, China.
Chen
Li-jun
LJ
Sun
Xiao-jing
XJ
Zhao
Guo-fa
GF
Cheng
Xiu-ying
XY
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000494:pharmacology* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D008854:Microscopy, Electron; D052016:Mucositis / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate
D000964:Antimetabolites, Antineoplastic; D017370:Interleukin-11; D018809:Proliferating Cell Nuclear Antigen; D008727:Methotrexate