Related Experiment Videos
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.
Insights
Polymyxin-B (PMB) effectively inhibits lipopolysaccharide (LPS)-induced interleukin-1 (IL-1) secretion from human monocytes, but its efficacy varies based on LPS origin. PMB
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Lipopolysaccharides (LPS) are potent immune activators produced by Gram-negative bacteria.
- Interleukin-1 (IL-1) is a key cytokine involved in inflammatory responses.
- Polymyxin-B (PMB) is an antibiotic known to bind and neutralize LPS.
Purpose of the Study:
- To investigate the efficacy of Polymyxin-B (PMB) in inhibiting lipopolysaccharide (LPS)-induced interleukin-1 (IL-1) secretion by human monocytes.
- To determine if the inhibitory effect of PMB on IL-1 secretion is dependent on the bacterial source of LPS.
Main Methods:
- Human monocytes were cultured in vitro.
- LPS from various bacterial species (e.g., Escherichia coli, Neisseria meningitidis) was used to induce IL-1 secretion.
- Interleukin-1 (IL-1) levels were quantified using a comitogenic assay with mouse thymocytes.
- The effect of varying concentrations of PMB on LPS-induced IL-1 secretion was assessed.
Main Results:
- PMB completely inhibited IL-1 secretion induced by LPS from Escherichia coli and Acinetobacter calcoaceticus.
- PMB showed limited or no inhibition of IL-1 secretion induced by LPS from Neisseria gonorrheae, Neisseria meningitidis, Bordetella pertussis, and Salmonella enteritidis.
- Inhibition of Neisseria meningitidis LPS-induced IL-1 was only achieved at very low PMB concentrations and was less effective in the presence of serum.
- High concentrations of PMB alone could stimulate IL-1 secretion and act synergistically with LPS.
Conclusions:
- The inhibitory effect of Polymyxin-B (PMB) on LPS-induced IL-1 secretion is highly dependent on the specific lipopolysaccharide (LPS) source.
- PMB's effectiveness is influenced by factors such as LPS concentration, bacterial origin, and the presence of serum.
- These findings have implications for understanding LPS-mediated inflammation and the potential use of PMB in detecting endotoxin contamination.