Interleukin-1 does not stimulate DNA synthesis of cultured human keratinocytes growth-arrested in...

Interleukin-1, a multifunctional cytokine, plays a central role in inflammatory processes. Several reports have appeared demonstrating that IL-1 stimulates growth of keratinocytes under certain experimental conditions, and we have shown previously that it can act as a strong stimulator of DNA synthesis in murine keratinocytes that have been growth-arrested by removal of growth factors (GF) from the medium for several days. Using the same assay system, we report here that, in contrast to cultured mouse keratinocytes, growth-arrested adult and newborn human keratinocytes do not respond to IL-1 with an increase in DNA synthesis. The experiments were performed with primary and secondary cells and cells propagated with and without feeder layer prior to the assay. A growth response to IL-1 in the absence of exogenous GF was only observed in non-growth-arrested human keratinocytes, i.e., when the cytokine was added for 24 to 48 h immediately after removal of other GF from the culture. Because keratinocytes continue to grow during this time anyway, although at a reduced rate, the additional growth observed with IL-1 could be explained as an enhancement of the growth-promoting effect by factors not previously completely removed from the culture. We would like to conclude from our results that, contrary to the findings in cultured mouse keratinocytes, IL-1 has no direct mitogenic effect on cultured human keratinocytes, but can still act as a growth promoter under certain conditions, apparently in concert with other GF.