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Oedema formation in acute inflammation in the rabbit and the effects of glucocorticosteroids

Yarwood, Helen; (1994) Oedema formation in acute inflammation in the rabbit and the effects of glucocorticosteroids. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

A characteristic feature of acute inflammation is increased microvascular permeability. Mediators that increase microvascular permeability can act in 2 ways; either directly on the endothelial cell eg. bradykinin, or by a mechanism dependent on circulating neutrophils eg. the chemoattractant FMLP. Oedema can be suppressed by both steroid and non-steroid anti-inflammatory drugs. These compounds may be able to act at several levels. This study was designed to investigate mechanisms of oedema formation and the possible sites of action of anti-inflammatory compounds. FMLP-induced oedema formation was not dependent on endogenous histamine release or pro-inflammatory products of the cyclo-oxygenase pathway. Intravenous infusion of zymosan-activated plasma produced transient neutropenia in rabbits which resulted in inhibition of oedema formation induced by FMLP, but not that induced by bradykinin. Ibuprofen, selectively inhibited FMLP-induced oedema formation when administered intravenously. This drug did not induce neutropenia and the effect was independent of cyclo-oxygenase inhibition. Ibuprofen may interfere with the interaction between circulating neutrophils and venular endothelial cells. The microtubule blocking agent colchicine also selectively inhibited FMLP- induced oedema formation even when it was administered at intervals after intradermal FMLP. This suggests that continuing interactions between functionally active neutrophils and endothelial cells are necessary for the protracted plasma protein leakage induced by this chemoattractant. There is evidence that anti-inflammatory steroids may owe some of their anti-inflammatory actions to effects on the target cells of inflammatory mediators eg. microvascular endothelial cells 2md neutrophils. In an attempt to investigate this possibility in vivo the ability of dexamethasone to modulate oedema formation and ¹¹¹In-neutrophil accumulation in rabbit skin was investigated. Dexamethasone was effective when administered in three ways. Firstly, local pretreatment of skin with dexamethasone inhibited oedema responses but not ¹¹¹In-neutrophil accumulation. Secondly, treatment of neutrophil recipient rabbits intravenously with dexamethasone inhibited both oedema responses and ¹¹¹In-neutrophil accumulation in response to exogenous chemoattractants. Thirdly, systemic treatment of neutrophil donor animals with dexamethasone resulted in suppression of ¹¹¹In-neutrophil accumulation in response to intradermal chemoattractants in recipients. Systemic treatment with dexamethasone suppressed neutrophil accumulation oedema formation and the generation of LTB₄ induced by intraperitoneal-injection of zymosan in the rabbit. The generation of TXB₂ and prostacyclin were not inhibited by dexamethasone. Depleting animals of circulating neutrophils inhibited the generation of LTB₄ suggesting that accumulating neutrophils are responsible for the generation of this chemoattractant. This study shows that anti-inflammatory compounds can inhibit oedema formation and neutrophil-accumulation by acting at several different sites. There is evidence for inhibition by effects on the microvascular endothelial cell and the neutrophil.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Oedema formation in acute inflammation in the rabbit and the effects of glucocorticosteroids
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10106681
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