DIFFERENTIAL-EFFECTS OF INTERLEUKIN-1-BETA AND INTERLEUKIN-2 ON GLIA AND HIPPOCAMPAL-NEURONS IN CULTURE

The present study was undertaken to assess the effects of interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2) on glial and neuronal cells in culture. The presence of IL-1 beta-like and IL-2-like immunoreactivity was detected in media collected from both astroglial and microglial cultures, indicating that both lymphokines can be released from either cell type. However, the levels measured in microglial media were significantly higher than in the astroglial media. Moreover, the content of IL-1 beta-like immunoreactive material in the media was approximately five- to 10-fold greater than that of IL-2, although exposure of both microglial and astroglial cultures to IL-1 beta significantly enhanced this measure. A possible role for this glial-derived IL-1 beta as an astroglial growth factor was substantiated by experiments showing that the lymphokine increased the incorporation of [H-3]thymidine into astroglial, but not microglial cultures. In contrast, 1L-2 did not significantly alter glial proliferation. In hippocampal neuronal cultures, these lymphokines affected neuronal survival differently. Thus, only the highest concentration (500 ng/ml) of IL-1 beta tested decreased the long-term (three day), but not the short-term (one day), survival of these neurons, whereas neuronal survival was compromised by IL-2 even after short-term (one day) exposure. In addition, in the long-term (three-day-old) neuronal cultures exposed to IL-2, extensive cellular swelling, vacuolations and neurite retractions were noted, even in cultures exposed to relatively low concentrations (<10 ng/ml) of the lymphokine. These effects were not apparent with IL-1 beta or the other lymphokines tested, including IL-3, IL-4 and IL-8. The results suggest that the glial-derived lymphokines IL-1 beta and IL-2 may have different functions in the CNS. Whereas IL-1 beta may have an important role in the developing brain as a maintenance and growth-promoting factor, IL-2 may function as an inhibitory factor, and may be of significance only in instances during which it accumulates in sufficiently high concentrations in the vicinity of neurons.