We examined the biological effects induced by both human recombinant interleukin-1 alpha (IL-1 alpha) and beta (IL-1 beta) in five different cell types of human, rat and mouse origin. IL-1 alpha and beta preparations were standardized in terms of biological activity in the EL-4/CTLL bioassay and, in parallel, employed to stimulate PGE2 secretion in human fibroblasts, mesangial cells (MC), C57B1/6 mouse MC, DBA/2 mouse macrophages and Sprague Dawley rat MC. In addition, the co-mitogenic effects of IL-1 alpha and beta were determined in freshly prepared Sprague Dawley rat thymocytes. No significant differences in IL-1 alpha and beta concentration dependent PGE2 production were detectable in the different cell types (MC, fibroblasts and macrophages) of human or mouse origin. Incubation of Sprague Dawley rat MC with both IL-1 alpha and beta resulted in a concentration dependent production of PGE2. However, in contrast to mouse or human MC the potency of IL-1 beta to induce PGE2 in Sprague Dawley rat MC was 26-fold higher compared to IL-1 alpha. In addition, the potency of IL-1 beta to enhance co-stimulated proliferation of Sprague Dawley thymocytes was 200-fold higher than that of equal biological activities of IL-1 alpha. When we tested the additive effects on Sprague Dawley cells, increasing IL-1 beta concentrations added to a fixed IL-1 alpha concentration resulted in a cumulative rise in both, PGE2 secretion by MC and thymocyte proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

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The NF kappa B heterodimer/homodimer balance and IL-1-stimulated IL-2 production in murine T lymphocytes.

Activation of NF kappa B is considered one way IL-1 exerts its costimulatory effect on T cell activation and IL-2 production. However, T helper 2 cells do not synthesize IL-2 upon IL-1 stimulation, although they depend on IL-1 for proliferation. The involvement of NF kappa B in IL-2 production was therefore addressed in two different murine cell lines: D10N, a T helper 2 cell line that does not synthesize IL-2, and EL4 6.1., a thymoma cell line producing IL-2 when stimulated with IL-1. In both cell types IL-1 activated the DNA binding activity of the NF kappa B heterodimers p50/65 and p50/c-rel via the IL-1 type I receptor. In D10N cells, however, the p50/p50 homodimer is present in large amounts in unstimulated cells, whereas the heterodimers were only activated by IL-1-treatment. In contrast, only marginal amounts of the p50/p50 homodimer were found in EL4 6.1. cells, but a strong activation of heterodimers was induced by IL-1. The findings are compatible with the concept of p50 homodimer being inhibitory by replacing the p50/p65 or p50/c-rel heterodimer from nuclear kappa B binding sites. The inability of D10N cells to respond to IL-1 exposure with IL-2 formation might therefore be due to their high constitutive levels of p50 homodimers.

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