The innate immune system is the first line of defense against infection. Its response to pathogens is mediated primarily through phagocytic cells. These cells recognize and respond to pathogens with an inflammatory cascade involving production of cytokines and other molecules. Activation of the innate immune response occurs through pathogen recognition receptors (PPRs) that recognize and bind pathogen-associated molecular pattern (PAMP) domains of foreign microorganisms. We utilized the THP-1 monocyte/macrophage cell line to study the activation of the innate immune system by lipopolysaccaride (LPS), a common PAMP associated with gram-negative bacteria. Cell activation was detected by measuring the levels of secreted tumor necrosis factor a (TNFa), a proinflammatory cytokine. Increased levels of TNFa were observed in monocytes treated with LPS compared to controls. Furthermore, experiments confirmed a sensitive dose-dependent effect of LPS on monocyte TNFa production with an EC50 value of 0.15 mg/ml. Simultaneous treatment with 1 mg/ml polymyxin-B (PMX-B), an LPS antagonist, completely neutralized the response induced by low concentrations of LPS (0.01-0.1 mg/ml). The effect of this PMX concentration at higher LPS concentrations (0.3-10 mg/ml) revealed the competition between LPS and PMX for the same binding site. Our data verified the sensitivity of THP-1 monocytes to PAMPs and supports their use as an effective cell model system for investigating other potential activators of the innate immune response including the amyloid beta peptide (Ab) in Alzheimer's disease.