Studies of IL 1 production have established that endotoxin- stimulated human monocytes rapidly synthesize, accumulate intracellularly and partly release IL 1 into culture media. Intracellular IL 1 is located mostly in the cytosol of monocytes and precursor IL 1 alpha but not IL 1 beta is phosphorylated exclusively at serine residues. Phosphorylation promotes enzyme cleavage and the plasma-membrane binding capacity of precursor-IL 1 alpha. We have studied post-receptor events and have determined that IL 1 rapidly phosphorylates 65 and 74 kDa cytosolic proteins at serine residues in glucocorticoid pretreated human PBMC. We have further investigated the basis for the growth inhibitory/cytocidal effect of IL 1 on several types of human tumor cell lines. Both in cells that are activated by IL 1 or that undergo cytocidal processes, IL 1 regulates a rate-limiting enzyme for polyamine synthesis, ornithine decarboxylase and induces a mitochondrial associated 25 kDa superoxide dismutase moiety. We have purified novel neutrophil chemotactic factor (NCF) to homogeneity and determined the partial amino acid sequence. Based on the protein sequence, the cDNA was cloned and the complete nucleotide sequence for NCF was determined and amino acid sequence deduced. Both IL 1 and tumor necrosis factor both induce mRNA for NCF activity in human PBMC.
