Interleukin-8 potentiates the effect of interleukin-1-induced uterine contractions

Hum Reprod. 1999 Feb;14(2):560-5. doi: 10.1093/humrep/14.2.560.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology
  • Dinoprostone / blood
  • Drug Combinations
  • Drug Synergism
  • Endometrium / cytology
  • Endometrium / physiology
  • Female
  • Humans
  • Interleukin-1 / pharmacology*
  • Interleukin-8 / pharmacology*
  • Neutrophils / physiology
  • Rabbits
  • Recombinant Proteins
  • Uterine Contraction / physiology*
  • Uterus / drug effects*
  • Uterus / physiology

Substances

  • Drug Combinations
  • Interleukin-1
  • Interleukin-8
  • Recombinant Proteins
  • Dinoprostone