The interleukin-1 system in the testis

The interleukin-1 (IL-1) family consists of two agonist proteins, IL-1 alpha and IL-1 beta, and one antagonist, IL-1 receptor antagonist (IL-1ra), which blocks the action of the agonists by binding and competing at the IL-1 receptor level. IL-1 beta and to a lesser extent IL-1 alpha were originally described as rapidly inducible proinflammatory cytokines released by activated macrophages. However, IL-1 alpha has been found to be constitutively produced by certain tissues, and noninflammatory functions have been proposed for this protein, although they have not yet been well elucidated. Consistent with this suggestion, we previously showed that the intact rat testis constitutively produces large amounts of IL-1 alpha at both the mRNA and protein levels. The expression of IL-1 alpha was found to be confined to Sertoli cells, with evidence of a developmental as well as a stage-dependent production pattern. In more recent studies, we have found indications that the testis can also initiate production of IL-1 beta upon stimulation with inflammatory inducers such as endotoxin. Further, we have detected constitutive testicular expression of IL-1ra, opening up the possibility that IL-1 action in the testis may be specifically regulated by paracrine mechanisms. Recent data have demonstrated that the testis can produce more than one isoform of IL-1 alpha with indications of both post-transcriptional and post-translational modifications, resulting in at least three distinct bio- and immunoreactive IL-1 alpha proteins. We conclude that all three classical IL-1 ligands and novel IL-1 alpha isoforms are present in the testis and may serve as paracrine mediators under physiological or pathophysiological conditions. The function of this testicular IL-1 agonist-antagonist network is a current focus of investigation.