To determine the effect on detection in PBMC in the most highly differentially expressed monocyte genes, genes were ranked by fold change in the Mono+ sample and the most differentially expressed genes were selected. Detection of these genes in PBMC was investigated by selecting different numbers of the topmost differentially expressed genes: from the top 10 genes to the top 1000 genes. As an example, all of the 100 monocyte genes most differentially expressed in response to LPS were detected in PBMC at 3 hours, and 96 of the top 100 monocyte genes at 24 hours. The proportion of genes detected in PBMC decreased with increasing numbers of genes selected, confirming that magnitude of Trichostatin A expression in monocytes affected detection in PBMC. This seems to be followed by direct activation of NFkB and “priming” of macrophages, leading to an increased baseline production of proinflammatory mediators. Upon a “second hit”, such as exposure to LPS, IgG-IC or other inflammatory stimuli, the inflammatory response is greatly accentuated. Another possibility might be a compensatory overactivity of pulmonary sympathetic nerve endings or increased catecholamine production by lymphocytes, resulting in increased norepinephrine levels in BAL fluids. However, we recently demonstrated in the present model of ALI that neither T cells nor sympathetic nerves are involved in events leading to ALI, but, rather, alveolar macrophages and neutrophils are responsible for increased catecholamine levels in BAL fluids following IC-ALI. Moreover, in a recent study, untreated and healthy bilaterally adrenalectomized rats displayed morphological signs of renal inflammation when compared to untreated adrenal-intact littermates , confirming our findings that adrenalectomized rats exhibit a certain proinflammatory priming. Thus, it is now becoming evident, that the sympathetic nervous system may play a dualistic role during the inflammatory response, than previously thought. While it clearly has profound anti-inflammatory effects during systemic inflammation as described above , we are now beginning to understand that the local inflammatory response can be immensely boosted through local, cell-dervied catecholamine production and subsequent adrenergic signaling in various immune cells. This is also illustrated by relating the proportion of LPSinduced gene expression changes in monocytes detectable in PBMC to their fold change. The expression of a number of specific individual genes involved in the immune response to LPS was investigated further to compare expression in different cell types. First, the expression of ‘validation’ genes encoding cytokines likely to be differentially expressed in monocytes in response to LPS on the basis of previous published data was investigated. The expression of interleukin -1a, IL-1b, IL-6 and IL-10 genes was upregulated as expected, with expression after 3 hours’ LPS stimulation being more upregulated than after 24 hours.