Neutralization of Cytokine Activity at the Receptor Level Improves Sperm Motility in Men With Spinal Cord Injuries

Abstract

Men with spinal cord injury (SCI) have a unique semen profile characterized by normal sperm concentrations but abnormally low sperm motility. Previous studies showed that elevated concentrations of cytokines in the seminal plasma of these men contribute to this condition. For example, when elevated concentrations of interlekin-1b (IL-1b), IL-6, and tumor necrosis factor-a (TNF-a) were immunoneutralized in the semen of men with SCI, sperm motility improved. The present study investigated if these cytokines act on sperm cell receptors to inhibit sperm motility. Semen was collected from men with SCI and from healthy non-SCI men. Sperm were separated from the seminal plasma by centrifugation. Eight identical aliquots of 5000 sperm suspended in 50 mL of seminal plasma were prepared for each subject. Agents were added to the aliquots in order to neutralize IL-1b, IL-6, and TNF-a at the receptor level. In SCI subjects, sperm motility improved in each treatment group compared with the untreated group, but statistical significance was reached only when neutralizing agents to all 3 cytokines were added. Improvement was less pronounced in subjects with close to normal semen cytokine concentrations or close to normal pretreatment sperm motility. In control subjects, IL1b, IL-6, and TNF-a were within normal values, and addition of receptor blockers to semen had no effect on sperm motility. These data support the hypothesis that cytokines act at the level of the sperm receptor to inhibit sperm motility. These data further support the notion that inactivating semen cytokines leads to improved sperm motility in SCI men. Our goal is to develop this finding into a treatment for low sperm motility in men with SCI.Key words: Infertility, ejaculation, semen, TNF-a, IL-1b, and IL-6. J Androl 2007;28:717-721 M en with spinal cord injury (SCI) have a unique semen profile characterized by normal sperm concentration but abnormally low sperm motility (Brackett et al, 1996(Brackett et al, , 1997DeForge et al, 2005;Brown et al, 2006). Factors in the seminal plasma contribute to this condition. For example, previous studies showed elevated concentrations of white blood cells and activated T-cell subpopulations in the semen of men with SCI (Basu et al, 2002). Additionally, elevated concentrations of cytotoxic cytokines were found in the seminal plasma of these men . When the elevated cytokine concentrations were immunoneutralized with monoclonal antibodies added to the semen, sperm motility improved (Cohen et al, 2004).The present study was undertaken to determine if cytokine receptors are involved in mediating the effects of cytokines on sperm motility in men with SCI. Materials and Methods SubjectsSubjects were men with traumatic SCI and healthy non-SCI subjects. All subjects were participants in the Male Fertility Research Program of the Miami Project to Cure Paralysis at the University of Miami Miller School of Medicine, Miami, Fla. The mean (6 SEM) age of SCI subjects was 31.9 6 2.3 years (range, 20-42). All SCI subjects were ...

The Novel Human β-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss

“…Cytokines in the semen have physiological and pathological functions. Men with spinal cord injury have unique semen with normal sperm concentrations but abnormally low sperm motility because their elevated levels of the cytokines IL-1␤, IL-6, and TNF-␣ act at the level of the sperm receptor to inhibit sperm motility (42). TNF-␣ and IL-6 significantly reduce progressive motility at higher concentrations in a dose-and time-dependent manner (43).…”

Comparison of in vitro fertilization/intracytoplasmic sperm injection outcomes in male factor infertility patients with and without spinal cord injuries

“…The most common abnormalities include low sperm motility, low sperm viability, leukocytospermia, and high sperm DNA fragmentation (3)(4)(5)(6)11). Although the cause of these semen abnormalities is unknown, there is evidence that inflammatory processes in the semen contribute to the problem (12)(13)(14). Accessory gland dysfunction due to SCI-related dysinnervation may also contribute to the observed abnormalities (15)(16)(17).…”

Fresh testicular sperm retrieved from men with spinal cord injury retains equal fecundity to that from men with obstructive azoospermia via intracytoplasmic sperm injection

“…However, even if ejaculated sperm are obtained, the quality is usually poor in motility and viability, thus reducing the success rate of IUI (6, 7). The cytokines secreted in the semen by leukocytes are reportedly responsible for the reduced sperm quality (11). Another possible factor that reduces sperm quality is hypogonadotropism in patients with SCI (12); this phenomenon is explained by altered neural or hormonal pathways between the hypothalamus and the pituitary gland (13).…”