Ontogeny of lymphocyte activating factors in conventional and germfree rats

Immune regulatory cytokines have previously been demonstrated outside the immune system in, e.g., the skin, testis, and brain, and suggested to serve as barrier site defence mediators. We have recently demonstrated constitutive production of an interleukin-1 (IL-1)-like factor(s) in the proximal gastrointestinal tract, liver, and placenta of adult rats. In the present study we have investigated the developmental production of IL-1-like factors in these tissues in conventional rats and in rats raised under germfree conditions. Slight IL-1 bioactivity was detected at a gestational age of 18 days in the skin and esophagus, and on day 19 significant amounts were detected in the skin, tongue, esophagus, and stomach. The activity was maximal at gestational day 20-21, and stationary at all later time-points. The placenta and liver contained high amounts of IL-1 activity throughout fetal life. The brain showed a transient appearance of IL-1 bioactivity at a gestational age of 19-21 days, but no activity at later time-points. Germfree rats showed no significant difference in the ontogeny or amounts of IL-1 bioactivity compared to conventional rats. It can be concluded that the IL-1 bioactivity appears at a definite time point in all measured tissues in fetal life and that exposure to microbial antigens does not seem to influence its production. As the investigated tissues show a high proliferation rate, it is tempting to suggest that the detected IL-1 (-like factors) might have an alternate function in these tissues, e.g., to serve as growth factors.