The interleukin-1 system in the testis

The interleukin-1 (IL-1) family consists of two agonist proteins, IL-1 alph a and IL-1 beta, and one antagonist, IL-I receptor antagonist (IL-1ra), whi ch blocks the action of the agonists by binding and competing at the IL-1 r eceptor level. IL-1 beta and to a lesser extent IL-1 alpha were originally described as rapidly inducible proinflammatory cytokines released by activa ted macrophages. However, IL-1 alpha has been found to be constitutively pr oduced by certain tissues, and noninflammatory functions have been proposed for this protein, although they have not yet been well elucidated. Consist ent with this suggestion, we previously showed that the intact rat testis c onstitutively produces large amounts of IL-1 alpha at both the mRNA and pro tein levels. The expression of IL-1 alpha was found to be confined to Serto li cells, with evidence of a developmental as well as a stage-dependent pro duction pattern. In more recent studies: we have found indications that the testis can also initiate production of IL-1 beta upon stimulation with inf lammatory inducers such as endotoxin. Further, we have detected constitutiv e testicular expression of IL-1ra, opening up the possibility that IL-I act ion in the testis may be specifically regulated by paracrine mechanisms. Re cent data have demonstrated that the testis can produce more than one isofo rm of IL-1 alpha with indications of both post-transcriptional and posttran slational modifications, resulting in at least three distinct bio- and immu noreactive IL-1 alpha proteins. We conclude that all three classical IL-1 l igands and novel IL-1 alpha isoforms are present in the testis and may serv e as paracrine mediators under physiological or pathophysiological conditio ns. The function of this testicular IL-1 agonist-antagonist network is a cu rrent focus of investigation.