Expression of IL-8 gene in human monocytes and lymphocytes: Differential regulation by TNF and IL-1

TNF-alpha and IL-1 were reported to be the most powerful inducers of IL-8 i n a multitude of cells, including leukocytes, In this study, we investigate d TNF-alpha- and IL-1-mediated regulation of IL-8 gene expression in non-fr actionated PBMC, and purified monocyte (MO) and Lymphocyte (LY) fractions. Our analysis revealed that purified human MO did not respond to exogenous T NF-alpha with the induction of IL-8 mRNA or protein, nor require endogenous TNF-alpha for IL-8 expression. In contrast, in the presence of exogenous I L-1 alpha and IL-1 beta a substantial enhancement of IL-8 mRNA and protein expression in MO was observed. Nevertheless, antibodies to IL-1 alpha and I L-1 beta were unable to downregulate the expression of IL-8 in resting adhe rent or Staphylococcus aureas Cowan 1 (SAC)-stimulated MO. In contrast with MO, purified LY and non-fractionated PBMC expressed IL-8 in response to ex ogenous TNF-alpha, similar to exogenous IL-1 alpha and IL-1 beta, As was se en with MO, antibodies to TNF-alpha, IL-1 alpha and IL-1 beta did not inhib it the expression of IL-8 in purified LY and non-fractionated PBMC stimulat ed with SAC and LPS, Taken together, our data demonstrate major differences in responsiveness of MO and LY to exogenous TNF-alpha and IL-1, and sugges t relative autonomy of IL-8 gene expression in these cells that does not re quire accessory cytokines but can be induced directly by exogenous stimuli. (C) 2000 Academic Press.