Potential Therapeutic Use of Cytokines in Gynaecology and Obstetrics

Abstract

Therapeutic manipulation of cytokines may be accomplished by inhibition of a particular cytokine using an antagonist or by administering the cytokine itself. Cytokines appear to have a number of physiological roles, and consequently therapeutic implications, in obstetrics and gynaecology. In the central nervous system, interleukin-1 (IL-1) decreases gonadotropin releasing hormone and luteinising hormone levels and increases prolactin levels. Interferon-alpha and -gamma and tumour necrosis factor-alpha have negative effects on sperm motility and penetration rates. Seminal IL-6 and IL-8 levels correlate negatively with fertility. IL-8 seems to be involved in periovulatory events by attracting and activating neutrophils that play a role in timely follicular rupture. Leukaemia inhibitory factor has been shown to be essential for blastocyst implantation. Interleukin-1 may be one of the signals for the onset of human parturition, and may also play a role in the initiation of preterm labour associated with intra-amniotic infection. In a mouse model, pretreatment with subcutaneous IL-1 receptor antagonist (IL-1ra) prevented IL-1-induced preterm parturition, suggesting a role for the use of anticytokine agents in the treatment of infection-associated preterm labour. IL-8 induces cervical ripening when applied locally to the cervix in rabbits, which indicates its pivotal role in cervical maturation. The evaluation of cytokine levels, especially IL-1, may be used as a diagnostic tool to monitor osteoporosis, and drugs such as IL-1ra that interfere with cytokine action could provide new therapies for the effective management of postmenopausal osteoporosis. In spite of all these possibilities, current cytokine-based therapies are still experimental, and numerous problems need to be resolved before they are used in routine clinical applications.