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 plac ebo or experimental drugs in the form of vaginal suppositories. The supposi tories contained human recombinant IL-8 (200 ng), IL-1 (200 ng), IL-8 (200 ng) + IL-1 (200 ng) or vehicle (Witepsol base, 500 mu l). Subsequently, the plasma concentration of prostaglandin (PG) E-2 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 fr equency (P < 0.01, P < 0.0007) and amplitude (P < 0.0001) in an in-vitro ex periment 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 a ny contractions. Prostaglandin concentration was increased similar to 8-fol d with IL-8 + IL-1 (P < 0.0001) and 2.5-fold with IL-1 treatment (P < 0.000 1). Neutrophil numbers were significantly increased,vith IL-8 + IL-1 > IL-8 > IL-1 (P < 0.002, P < 0.0003 and P < 0.008) compared with vehicle. Our da ta suggest that IL-8 stimulates IL-1-induced uterine contractions through P GE(2) production and could be an important process during labour and delive ry.