The effect of Y-25510 injection on the serum levels of some cytokines in healthy adult volunteers.
OBJECTIVE
Y-25510 was administered by means of an intravenous drip infusion to healthy adult male volunteers at a dose of 40, 80 or 160 mg in a single-dose study, and at a dose of 160 mg once a day for 7 days in a multiple-dose study.


RESULTS
Serum levels of interleukin (IL)-1beta, IL-6 and IL-10 were significantly increased, but there was no change in leukocyte and platelet counts. The peak serum concentration of IL-1beta was nearly maximum at the single doses of 40 and 80 mg, and at the multiple dose of 160 mg per day. The peak serum concentration of IL-6 increased in a dose-dependent manner at a dose of 40 mg or more. For the multiple-dose study, the serum level of IL-10, which remained unchanged in the placebo group, began to increase in the Y-25510 group following the maximum serum level of IL-1beta and IL-6. There were no clinically relevant differences in body temperature and blood pressure after the administration of Y-25510.


CONCLUSIONS
These findings that leukocyte and platelet counts never increased, despite the increment of the IL-1beta and IL-6 production after the administration of Y-25510, may be explained in part by the negative feedback mechanism induced by IL-10.
Azuma
J
J
Clinical Evaluation of Medicines and Therapeutics, Faculty of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Ogura
M
M
Yamamoto
I
I
Hisadome
M
M
Fukuda
T
T
Ikeda
Y
Y
Mori
H
H
Oka
T
T
Asano
S
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D013997:Time Factors; D014838:Volunteers
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D011720:Pyrazoles; D011725:Pyridines; D016753:Interleukin-10; C078528:Y 25510