Effect of Cytokines on Sperm Motility and Ionophore—Stimulated Acrosome Reaction

Abstract

The effects of soluble products from leukocytes (WBC) on sperm motility and calcium ionophorestimulated acrosome reaction (AR) were examined. Supernatants of mononuclear WBC, isolated from peripheral blood and stimulated by the lectins Phyfolacca americana (pokeweed mitogen) or concanavalin A, caused a weak but significant inhibition of progressive sperm motility. The recombinant cytokine interferon-y (IFN-y) in high concentrations inhibited motility of sperm from 5 of 8 donors tested. The recombinant cytokines tumor necrosis factor-a (TNF-a) and interleukin-8 (IL-8) did not show any effect on sperm motility. Reactive oxygen species (ROS) produced by stimulation of polymorphonuclear WBC with a phorbol ester (PMA) tended to inhibit sperm motility. Neither supernatants from lectin-stimulated mononuclear WBC, IFN-y, TNF-a, IL-8, nor ROS showed any significant effect on the ionophore-challenged AR. acrosome reaction, sperm motility, cytokines, reactive oxygen species, lectins, human KeywordsHigh concentration of leukocytes in semen may be a causative mediator of otherwise unexplained infertility [ 151. Cytokines produced by these cells could be responsible for the effect. Thus, in a few studies an inhibiting role has been found of the cytokines interferon-? (IFN-y) and tumor necrosis factor-a (TNF-a) on motility of human sperm [ 14, 181 and on penetration rate in the hamster oocyte test [17],The cytokine interleukin-8 (IL-8) stimulates chemotaxis of human polymorphonuclear granulo-

Nonsperm Cells in Human Semen: With Special Reference to Seminal Leukocytes and their Possible Influence on Fertility

“…Thus, the percentage of motility was significantly decreased when spermatozoa were incubated with lo6 activated PMN/mL for 5 h. At 5 x lo6 activated PMN/mL there were decreases in three of four motility parameters studied: the percentage of motility, the curvilinear velocity, and the amplitude of lateral head displacement. A less pronounced inhibition of motility was observed by Fedder and Ellermann-Eriksen [37], which might be explained by the longer incubation time (1 8 h) used if the effect is reversible. Vogelpoel and Verhoef [86] found that PMN is activated for up to 4-6 h after stimulation with phorbol myristate acetate (PMA), while PMA-stimulated PMN were no longer active after 18 h.…”

“…Eisermann et al [3 11 could detect a significant inhibitory effect on motility at about 100 times lower concentrations. In other studies it was not possible to detect any effect at all of TNF-a on motility (Table 5 ) [37,42,481; nor did TNF-a in combination with low concentrations of interleukin-1 (IL-I) or interferon-y (IFN-y) show any inhibition of motility [42]. The varying results concerning the effect of TNF-a on sperm motility might be due to differences in sensitivity of sperm from different donors (compare IF"-y below) and differences in biological activity of the TNF-a solutions used.…”

“…Therefore, for recording of a possible negative influence on acrosome reaction, it has been necessary to use a strong acrosome reaction inducer (the calcium ionophore A23 187). However, with such an unphysiological induction of acrosome reaction, the lacking effect of supernatants from cultures of mononuclear WBC and of IFN-y and other cytokines on acrosome reaction in this system [37], an influence of such cytokines on capacitation and acrosome reaction in vivo cannot be excluded.…”

“…The PMN chemotactic factor interleukin-8 (IL-8) did not inhibit sperm motility (Table 6) [37], but preliminary data suggest that IL-8, even in low concentrations (5 ng/mL), can stimulate sperm hyperactivation (Figure 1). This is close to physiological IL-8 concentrations, which in semen from normal men has been recorded to about 2 ng/mL [76].…”

“…IFN-y inhibited sperm motility (Table 6) [37, 461 and sperm-oocyte fusion in the zona-free hamster oocyte assay [45] when used in high concentrations. A possible explanation why one group was not able to detect a motility-inhibiting effect of IFN-y, in combination with either IL-1 or TNF-a at low concentrations [42], may be an interindividual variation in sensitivity among sperm from different donors [37].…”