Interleukin-8 potentiates the effect of interleukin-1-induced uterine contractions.
The aim of this research was to study the effect of exogenous interleukin (IL)-8, IL-1 and IL-8 + IL-1 on uterine contractions in rabbits. Four equal groups of non-pregnant rabbits (n = 24) were investigated using either placebo or experimental drugs in the form of vaginal suppositories. The suppositories contained human recombinant IL-8 (200 ng), IL-1 (200 ng), IL-8 (200 ng) + IL-1 (200 ng) or vehicle Witepsol base, 500 microliters). Subsequently, the plasma concentration of prostaglandin (PG) E2 was estimated 3 h after the last dose of treatment. Neutrophil infiltration in the endometrial tissue was studied with anti-rabbit RT2 staining. Suppositories with IL-1 and IL-8 + IL-1 produced contractile responses with increased frequency (P < 0.003, P < 0.0005) and amplitude (P < 0.0001) in vivo, compared with vehicle. IL-1 and IL-8 + IL-1 also caused similar contractile effects with increased frequency (P < 0.01, P < 0.0007) and amplitude (P < 0.0001) in an in-vitro experiment than vehicle. The frequency and amplitude of uterine contractions were more significant with IL-8 + IL-1 than that of IL-1, both in vivo (P < 0.002, P < 0.05) and in vitro (P < 0.005, P < 0.01). IL-8 did not induce any contractions. Prostaglandin concentration was increased approximately 8-fold with IL-8 + IL-1 (P < 0.0001) and 2.5-fold with IL-1 treatment (P < 0.0001). Neutrophil numbers were significantly increased with IL-8 + IL-1 > IL-8 > IL-1 (P < 0.002, P < 0.0003 and P < 0.008) compared with vehicle. Our data suggest that IL-8 stimulates IL-1-induced uterine contractions through PGE2 production and could be an important process during labour and delivery.
Khatun
S
S
Department of Obstetrics and Gynaecology, Hamamatsu University School of Medicine, Shizuoka Prefecture, Japan.
Kanayama
N
N
Md Belayet
H
H
Yonezawa
M
M
Kobayashi
T
T
Terao
T
T
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D015232:Dinoprostone / Q000097:blood; D004338:Drug Combinations; D004357:Drug Synergism; D004717:Endometrium / Q000166:cytology / Q000502:physiology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits; D011994:Recombinant Proteins; D014590:Uterine Contraction / Q000502:physiology*; D014599:Uterus / Q000187:drug effects* / Q000502:physiology
D004338:Drug Combinations; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins; D015232:Dinoprostone