Direct stimulation of monocyte release of interleukin 1 by mycobacterial protein antigens

We examined stimulation of monocyte (MN) release of interleukin 1 (IL 1) by soluble microbial products. MN from tuberculin skin test nonreactive donors incubated with PPD (100 micrograms/ml) released IL 1 activity of 80.5 +/- 33.9 U/ml (mean +/- SD, n = 6), similar to that induced by optimal concentrations of LPS (76.4 U/ml). OKT3-reactive cells were not required for this process. PPD-stimulated IL 1 release by MN did not appear to be due to endotoxin contamination, as 1) PPD contained 0.01% endotoxin, 2) MN incubated in LPS (0.1 micrograms/ml) produced 19.5 +/- 13.9 U/ml, significantly less than PPD (p = 0.03), and 3) addition of polymyxin B (12.5 micrograms/ml) abrogated IL 1 production in response to LPS (0.1 microgram/ml) but had no significant effect on PPD induction of IL 1. Antigen 5, a partially purified cytoplasmic antigen of Mycobacterium tuberculosis, had similar IL 1-inducing effects. Arabinogalactan (a mycobacterial polysaccharide), streptolysin O, and tetanus toxoid did not. Thus, mycobacterial protein antigens directly stimulate MN to release IL 1. This property may be central to the response of the naive host to mycobacterial infection and may play a pathophysiologic role in tuberculosis.