Intravascular release of platelet activating factor in children with sepsis

Bussolino, Federico; Porcellini, M; Varese, L A; Bosìa, Amalia

doi:10.1016/0049-3848(87)90396-3

Cited by 50 publications

(19 citation statements)

References 4 publications

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“…PAF is reported to contribute to hemodynamic instability and organ or cellular dysfunction in a wide range of human [1][2][3][4], animal [5][6][7][8], and in vitro [9,10] models of sepsis or systemic inflammation. The organ that seems to be most susceptible to the consequences of PAF is the lung.…”

Section: Introductionmentioning

confidence: 99%

Platelet-Activating Factor and Bacteremia-Induced Pulmonary Hypertension

Clavijo¹,

Carter²,

Matheson³

et al. 2000

Journal of Surgical Research

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Section: Introductionmentioning

confidence: 99%

Platelet-Activating Factor and Bacteremia-Induced Pulmonary Hypertension

Clavijo¹,

Carter²,

Matheson³

et al. 2000

Journal of Surgical Research

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“…The recent observation that PAF is produced dur ing endotoxemia [45,46] and is released in the plasma of patients affected by sepsis [47] suggests that the clinical manifestations of sepsis may be caused by the release of PAF by EC stimulated with TNF and IL-I, two well-known mediators of endotoxic shock.…”

Section: Biologic Significance O F Pa F Produced By Ecmentioning

confidence: 99%

Role of Cytokines and Platelet-Activating Factor in Microvascular Immune Injury

Braquet

Hosford

Braquet

et al. 1989

Int Arch Allergy Immunol

102

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Inflammation is usually a tightly controlled process which confines tissue damage, prevents infection, and assists in cellular regeneration. However, if the inflammatory response becomes unregulated, this normally beneficial local event may escalate into a wider malignant activity, characterized by endothelial injury, excessive cell infiltration, and vascular leakage. Due to the ability of platelet-activating factor and tumor necrosis factor to elicit the release of each other, ‘prime’ cell responses, and influence the activity of other cytokines, we propose that these two mediators play a pivotal role in the formation of deleterious feedback cycles leading to the above endothelial damage which may underlie pathologies such as shock, sepsis, ischemia, and asthma. Platelet-activating factor antagonists such as BN 52021 inhibit the priming and other effects induced by platelet-activating factor and thus may be of therapeutic value in such conditions.

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“…Proinflammatory cytokines and platelet-activating factor (PAF) are generated in large amounts during the septic response (1). PAF, an ether-linked phospholipid, is one of the most hypotensive and inflammatory agents yet discovered (1,2,3,7). The effects of PAF are mediated through specific PAF receptors.…”

mentioning

confidence: 99%

A Double-Blind Placebo-Controlled Study of an Infusion of Lexipafant (Platelet-Activating Factor Receptor Antagonist) in Patients with Severe Sepsis

Suputtamongkol

Intaranongpai

Smith

et al. 2000

Antimicrob Agents Chemother

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Platelet-activating factor (PAF) is a potent endogenous proinflammatory mediator implicated in the pathogenesis of septic shock. A double-blind randomized placebo-controlled trial of an intravenous PAF receptor antagonist (lexipafant) was conducted with 131 adult Thai patients with suspected severe sepsis (66 of whom had positive blood cultures). Detailed serial clinical, biochemical, and cytokine measurements were performed. Lexipafant treatment was well tolerated. The 28-day mortality in the lexipafant group (61.4%) was similar to that in the placebo group (62.6%). There was also no evidence that lexipafant affected clinical or biochemical measures of disease severity or the profile of sequentially measured plasma cytokine levels. PAF may not have an important role in the pathogenesis of severe sepsis.Despite significant advances in antimicrobial treatment and intensive care support, sepsis remains a difficult medical management problem with mortality rates between 30 and 50% (5, 11). Proinflammatory cytokines and platelet-activating factor (PAF) are generated in large amounts during the septic response (1). PAF, an ether-linked phospholipid, is one of the most hypotensive and inflammatory agents yet discovered (1, 2, 3, 7). The effects of PAF are mediated through specific PAF receptors. PAF is produced by a broad range of cell types, including monocytes, macrophages, eosinophils, and platelets as well as vascular, kidney glomerular, and gastrointestinal endothelial cells. A wide variety of mediators stimulate these cells to produce PAF; many of these mediators are secreted during the cytokine cascade associated with septic shock. These include tumor necrosis factor (TNF), thrombin, leukotrienes, and bradykinin. PAF has several biological actions characteristic of a proinflammatory agent. When administered systemically to animals, it produces many of the features of septic shock. In experimental septic shock, blocking either the proinflammatory cytokines TNF and interleukin 1 (IL-1) or lipid mediators such as PAF decreases the severity of the disease (12, 13). In one study, the PAF antagonist BN 52021 was shown to be a safe and promising treatment of patients with severe gram-negative sepsis (6).Lexipafant (BB-882; British Biotechnology Ltd., Watlington, Oxford, United Kingdom) is another newly developed PAF antagonist. Lexipafant was shown to be a potent antagonist of PAF in in vitro studies involving the inhibition of [ 3 H]PAF receptor binding and in a PAF receptor binding assay conducted on human platelet membranes. In the latter system, lexipafant bound to the receptor seven times more avidly than native PAF (unpublished data). We report here results of a randomized placebo-controlled study to evaluate the clinical safety and efficacy of lexipafant as an adjunct to the treatment of severe sepsis. Lexipafant has been shown to be well tolerated when given intravenously to volunteers, to patients with pancreatitis, and to patients with sepsis (unpublished data). MATERIALS AND METHODSStudy design and patient ...

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Intravascular release of platelet activating factor in children with sepsis

Cited by 50 publications

References 4 publications

Platelet-Activating Factor and Bacteremia-Induced Pulmonary Hypertension

Platelet-Activating Factor and Bacteremia-Induced Pulmonary Hypertension

Role of Cytokines and Platelet-Activating Factor in Microvascular Immune Injury

A Double-Blind Placebo-Controlled Study of an Infusion of Lexipafant (Platelet-Activating Factor Receptor Antagonist) in Patients with Severe Sepsis

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