Polymyxin-B inhibition of LPS-induced interleukin-1 secretion by human monocytes is dependent upon the LPS origin

Abstract

Polymyxin-B (PMB) is an antibiotic known to inhibit various biological activities induced by lipopolysaccharides (LPS). We have investigated the ability of PMB to inhibit LPS-induced interleukin-1 (IL-1) secretion by human monocytes in vitro. Interleukin-1 was assayed by the conventional comitogenic assay using mice thymocytes. Our data demonstrate that PMB (1-2 micrograms/assay)-mediated inhibition of LPS-induced IL-1 secretion depends on the origin of the LPS. Interleukin-1 secretions induced by Escherichia coli and Acinetobacter calcoaceticus LPSs, when used at 1 microgram/assay were completely inhibited by PMB, whereas those induced by Neisseria gonorrheae, Neisseria meningitidis, Bordetella pertussis, and Salmonella enteritidis LPSs were unaffected. Neisseria meningitidis, the most potent IL-1 inducer tested could be inhibited by PMB only at concns below 5 ng/assay; when the assay was performed in the presence of serum (0.2%) PMB could not completely inhibit Neisseria meningitidis LPS-induced IL-1 secretion at LPS doses as low as 100 pg/assay. Polymyxin B itself, at doses greater than 50 micrograms/assay, stimulated IL-1 secretion and acted synergistically with LPS to induce IL-1 secretion when used at 10 micrograms/assay. Potential relevance of Lipid A-mediated IL-1 secretion and the use of PMB to detect endotoxin contamination is discussed.