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-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) 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 5,000 sperm suspended in 50 microL of seminal plasma were prepared for each subject. Agents were added to the aliquots in order to neutralize IL-1beta, IL-6, and TNF-alpha 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, IL-1beta, IL-6, and TNF-alpha 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.