Inhibitory effect of corticosteroids on the secretion of tumour necrosis factor (TNF) by monocytes is dependent on the stimulus inducing TNF synthesis.

The cytokine tumour necrosis factor (TNF) is believed to be involved in the pathophysiology of several human disease states, both septic and non-septic. Different pathways of induction are involved in the generation ofTNF in these disease states. We therefore used four different stimulatory agents, lipopolysaccharide, phorbol myristate acetate, silica quartz, and anti-human IgG antibody to study the influence of the corticosteroids prednisolone and budesonide on the secretion of TNF by human monocytes. Both prednisolone and budesonide inhibited TNF secretion induced by these four stimulating agents in a different degree. Inhibition was strong when TNF secretion was induced by lipopolysaccharide or anti-human IgG antibody. A weaker inhibitory effect was observed when TNF secretion was induced by silica quartz. Only minimal inhibition of phorbol myristate acetate induced TNF secretion was observed. Furthermore, it is shown that inhibition is dependent on the dose of corticosteroid, but not or only minimally on the dose of stimulating agent, indicating that inhibition cannot be overcome by increasing the cell-activating stimulus. Finally, optimal inhibition of TNF secretion by corticosteroids is shown to be dependent on the presence of corticosteroids during the phase of cell stimulation.