Sivelestat, a Neutrophil Elastase Inhibitor, Reduces Mortality Rate of Critically Ill Patients

Hoshi, Kunihiko; Kurosawa, Shin; Kato, Masato; Andoh, Kohkichi; Satoh, Daizoh; Kaise, Atsushi

doi:10.1620/tjem.207.143

Cited by 28 publications

(15 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonetheless, these studies suggest that in vivo antagonism of serine protease activity may provide new therapeutic strategies in inflammatory diseases. Indeed, attempts have been made to suppress the activity of NE in hereditary emphysema (Dirksen et al, 1999;Doring, 1999), chronic obstructive pulmonary disease (COPD) (Luisetti et al, 1996;Ohbayashi, 2002), cystic fibrosis (Cantin et al, 2006;Doring, 1999;Martin et al, 2006), and the management of acute lung injury (Hoshi et al, 2005;Ono et al, 2007;Zeiher et al, 2004), all with varying results. To date, no inhibitors of serine proteases have been approved for use in patients as many practical problems associated with the synthesis and delivery of these agents still remain [Reviewed in (Chughtai and O'Riordan, 2004)].…”

Section: Discussionmentioning

confidence: 99%

Neutrophil serine proteases fine-tune the inflammatory response

Pham¹

2008

The International Journal of Biochemistry & Cell Biology

217

178

View full text Add to dashboard Cite

Neutrophil serine proteases are granule-associated enzymes known mainly for their function in the intracellular killing of pathogens. Their extracellular release upon neutrophil activation is traditionally regarded as the primary reason for tissue damage at the sites of inflammation. However, studies over the past several years indicate that neutrophil serine proteases may also be key regulators of the inflammatory response. Neutrophil serine proteases specifically process and release chemokines, cytokines, and growth factors, thus modulating their biological activity. In addition, neutrophil serine proteases activate and shed specific cell surface receptors, which can ultimately prolong or terminate cytokine-induced responses. Moreover, it has been proposed that these proteases can impact cell viability through their caspase-like activity and initiate the adaptive immune response by directly activating lymphocytes. In summary, these studies point to neutrophil serine proteases as versatile mediators that fine-tune the local immune response and identify them as potential targets for therapeutic interventions.

show abstract

Section: Discussionmentioning

confidence: 99%

Neutrophil serine proteases fine-tune the inflammatory response

Pham¹

2008

The International Journal of Biochemistry & Cell Biology

217

178

View full text Add to dashboard Cite

show abstract

“…Moreover, the mortality in patients with severe cases, with APACHE II scores of 30-34, was only 18.8% (Table 5). The low mortality rates may be due to multimodal patient management such as the treatment of AHRF and ALI/ARDS with similar approaches; e.g., the use of steroid drugs [25,26], a neutrophil elastase inhibitor [27], and continuous hemodiafiltration (CHDF). Many studies have found multiple organ failure to be the primary cause of ALI/ARDS [4,28,29], and our present results also showed that this was the primary cause of death within 30 days of onset.…”

Section: Discussionmentioning

confidence: 99%

A prospective cohort study of ALI/ARDS in the Tohoku district of Japan (second report)

et al. 2010

View full text Add to dashboard Cite

show abstract

“…10,11,[19][20][21] Recent studies have shown that sivelestat reduced and prevented tissue ischemia and reperfusion injury in several organs. 11,22) The beneficial effects of neutrophil elastase inhibitor on post-perfusion lung and ischemia-reperfusion and endothelial cell injuries have been demonstrated in several experiments.…”

Section: Discussionmentioning

confidence: 99%