Expression of human IL 1 alpha and beta messenger RNAs and IL 1 activity in human peripheral blood mononuclear cells.

Abstract

The macrophage-derived lymphokine interleukin 1 (IL 1) plays a critical role in modulating immune (cellular and humoral) and nonimmune responses. For example, the relative expression of IL 1 alpha and beta under various states may be crucial to the success of the immune system in response to infection. Until recently, a comparative study of IL 1 mRNA expression and IL 1 biological activity was not possible. We have cloned both IL 1 alpha and beta cDNAs and employed them as probes in Northern blot analysis to determine in mitogen-stimulated peripheral blood mononuclear cells the steady-state expression of their cognate mRNAs with respect to IL 1 activity. IL 1 was determined by the lymphocyte-activating factor (IL 1/LAF) and the mononuclear cell factor (IL 1/MCF) activities. In lectin-stimulated PBMC, maximum cell-associated activities whereas detected at 12 and 24 hr after stimulation whereas maximum extracellular activities appeared between 24-48 hr. In the same cultures, the kinetics of IL 1 mRNA steady-state expression were determined by Northern gel blot analysis with IL 1 alpha and beta cDNA probes. IL 1 mRNAs were undetectable in noncultured freshly isolated PBMC (time zero). Both IL 1 mRNAs appeared as early as 4 hr after lectin stimulation as did IL 1 beta mRNA in unstimulated cultures. Both IL 1 alpha and beta mRNA steady-state levels were barely detectable by 48 hr. At all time points, IL 1 mRNA levels were considerably lower in unstimulated cultures. IL 1 beta mRNA was always considerably more abundant than IL 1 alpha mRNA. The less abundant IL 1 alpha mRNA showed a decrease in its stead-state levels prior to the reduction in the levels of IL 1 beta mRNA. TNF alpha activity and mRNA were not detected under these culture conditions. Poly(A) + RNA injected into Xenopus oocytes revealed that the Northern blot detected IL 1 mRNAs were biologically active. To understand the precise nature of IL 1 in immune and nonimmune events, we felt it necessary to first study the kinetics of IL 1 mRNA steady-state levels with respect to its cell-associated and extracellular biological activities. The data presented here may allow for a better understanding of the etiology of various immune and nonimmune responses that are modulated through the expression of IL 1.