Lung injury modulators

Freeman, B.A., Turrens, J.F., Mirza, Z., Crapo, J.D. and Young, S.L. (1985). Modulation of oxidant lung injury by using liposome-entrapped superoxide dismutase and catalase. Fed. Proc. 44, 2591-2595. 

Table 2 shows the studies of a-chemokines and p-chemokines in lung fluids of patients with ARDS. These studies in humans are supported by a number of studies in experimental animals showing that inhibition of a- and p-chemokine function modulates the severity of acute lung injury in experimental systems. 

Immune modulation has also been used to enhance lung gene expression, predominantly inhibition of T-cell responses to administration of adenoviral vectors (9,22 26). Whether this proves to be a clinically safe and useful strategy, particularly in the setting of acute lung injury, has not been determined. 

Although inflammatory cytokine profiles differ depending on the skin models used (Ricketts et al., 2000 Sabourin et al., 2002), they were shown to be elevated in response to SM. In contrast, in guinea pig lungs exposed to 2-chIoroethyI ethyl sulfide (CEES) (a mustards analog), the inflammatory cytokine TNF-a was found to be markedly elevated (Das et al., 2003). The inflammatory cytokines exacerbate the effects of CEES (Stone et al., 2003), which would imply that there is an amplification of the initial injury by the mustards. Lipopolysaccharide (LPS), a ubiquitous entity in our environment, also upwardly modulates the damage that CEES inherently causes to cells (Stone et al., 2003). 

Boles etal. (2000) demonstrated that 12-0-tetradecanoylphorbol-13-acetate enhanced the adherence of U-937 cells to fibronectin matrices by increasing the expression of both the a - and Pr subunit mRNAs and the surface expression of the protein. Modulation of OsPi expression may be important for regulation of monocytic cell function in lung inflammation after injury. 

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