The local anti‐inflammatory action of dexamethasone in the rat carrageenin oedema model is reversed by an antiserum to lipocortin 1

Duncan, Gordon S.; Peers, Susan H.; Carey, Frank; Forder, Robert A.; Flower, Roderick J.

doi:10.1111/j.1476-5381.1993.tb13440.x

Cited by 46 publications

(21 citation statements)

References 21 publications

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“…A number of groups using different, highly specific anti-LC 1 antibodies has demonstrated reversal of the antipyretic [22], anti-ischaemic [47], anti-oedema [48] and antimigratory actions [20] of glucocorticoids in vivo. Similaly, in vitro, specific monoclonal anti-LCl anti bodies have been shown to quench the effects of glucocor ticoids on cell differentiation [24], cell growth [23] and pituitary hormone release [10].…”

Section: Discussionmentioning

confidence: 99%

Immunoneutralization of Lipocortin 1 Reverses the Acute Inhibitory Effects of Dexamethasone on the Hypothalamo-Pituitary-Adrenocortical Responses to Cytokines in the Rat in vitro and in vivo

et al. 1995

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Our recent studies suggest that lipocortin 1 (LC1), a potential mediator of the anti-inflammatory, antiproliferative and anti-fever actions of glucocorticoids in peripheral tissues, may also contribute to the powerful negative feedback actions of the steroids on the hypothalamo-pituitary-adrenal (HPA) axis. In the present study we have used (1) an in vitro model to examine the influence of a specific neutralizing monoclonal anti-LC1 antibody (anti-LC1 mAb) on the capacity of dexamethasone to suppress the cytokine-induced release of the 41-amino acid corticotropin-releasing factor (CRF-41) and arginine vasopressin (AVP) from the rat hypothalamus and (2) a passive immunization protocol to assess the contribution of LCI to the inhibitory actions of dexamethasone on the HPA responses to immunological (i.p. injection of interleukin 1β, IL-1β) and surgical (laparotomy under ether anaesthesia) stress. In vitro, Il-1α (0.2 ng/ml), IL-1β (0.5 ng/ml), IL-6 (10ng/ml) and IL-8 (1 ng/ml) each caused significant increases in the release of immunoreactive (ir)-CRF-41 and ir-AVP from hypo-thalami removed from rats adrenalectomized 10-12 days before autopsy; these responses were readily inhibited by preincubation of the tissue with dexamethasone (10-⁷M). The inhibitory actions of the steroid were attenuated and, in many instances, abolished by inclusion in the medium of a monoclonal anti-LCI antibody (LCI mAb, diluted 1:15,000); an isotype-matched control antibody (antispectrin α+β, diluted 1:15,000) was ineffective in this regard. IL-1α (0.2 ng/ml), IL-1β (0.5 ng/ml) and IL-6 (10 ng/ml) also initiated similar increases in the release of CRF-41 and AVP from hypothalami from intact rats which were effectively blocked by dexamethasone (10^–7M). However, although the inhibitory actions of the steroid on the pharmacologically evoked release of CRF-41 were specifically overcome by anti-LC1 mAb (diluted 1:15,000), the steroid blockade of AVP release was not. In vivo, rats pretreated with either a polyclonal anti-LC 1 antibody (anti-LCI pAb, 1 ml/day s.c. for 2 days) or a corresponding volume of a nonimmune sheep serum (NSS) responded to immunological (IL-1β, 3 µg/kg i.p.) or surgical (laparotomy under ether anaesthesia) trauma with significant increases in the serum ACTH and corticosterone concentrations. In the NSS-treated groups, dexamethasone (100 µg/kg), which had no effect on the prestress concentrations of ACTH and corticosterone in the blood, completely prevented the HPA responses to both IL-1β and laparotomy. The steroid treatment also abolished the HPA responses to laparotomy in rats pretreated with anti-LC1 pAb. By contrast, passive immunization against LC1 largely overcame the ability of dexamethasone to inhibit the hypersecretions of ACTH and corticosterone provoked by IL-1β (3 µg/kg i.p.). The results suggest that LC1 plays an important role in mediating the inhibitory actions of dexamethasone on the HPA responses to cytokines in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Immunoneutralization of Lipocortin 1 Reverses the Acute Inhibitory Effects of Dexamethasone on the Hypothalamo-Pituitary-Adrenocortical Responses to Cytokines in the Rat in vitro and in vivo

et al. 1995

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“…Neutralizing antibodies against AnxA1 impaired the anti-inflammatory effects of GCs on carageenininduced paw oedema (Duncan et al, 1993), ischaemia-reperfusion injury (D'Amico et al, 2000) and adjuvant-induced arthritis (Yang et al, 1999). Inflammatory responses of an AnxA1 null mouse strain were exaggerated (Chatterjee et al, 2005;Hannon et al, 2003;Warne et al, 2006;Yang et al, 2004), and cells derived from these mice overexpressed COX-2, IL-1β and -6 in response to pro-inflammatory stimuli (Croxtall et al, 2003;Damazo et al, 2006;Hannon et al, 2003;Yang et al, 2006;Yona et al, 2004;Yona et al, 2005), suggesting that AnxA1 is an endogenous inhibitor of inflammatory responses .…”

Section: A Clarkmentioning

confidence: 97%

Anti-inflammatory functions of glucocorticoid-induced genes

Clark

2007

Molecular and Cellular Endocrinology

238

193

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“…Most of the experiments demonstrating the involvement of LC1 in the anti-inflammatory action of exogenous glucocorticoids have been acute in nature, that is to say they have examined LC1-dependent changes in the inflammatory response within hours of giving dexamethasone (see for example Duncan et al, 1993). Few studies have addressed the question of whether synthesis and externalization of LC1, driven by the endogenous hormones of the HPA axis itself, is important in regulating inflammation and the inflammatory process in vivo.…”

Section: Introductionmentioning

confidence: 99%

Acute inflammatory response in the mouse: exacerbation by immunoneutralization of lipocortin 1

Perretti

Ahluwalia

Harris

et al. 1996

British J Pharmacology

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1 An immuno-neutralization strategy was employed to investigate the role of endogenous lipocortin 1 (LC1) in acute inflammation in the mouse. 2 Mice were treated subcutaneously with phosphate-buffered solution (PBS), non-immune sheep serum (NSS) or with one of two sheep antisera raised against LC1 (LCS3), or its N-terminal peptide (LCPSI), three times over a period of seven days. Twenty four hours after the last injection several parameters of acute inflammation were measured including zymosan-induced inflammation in 6-day-old air-pouches, zymosan-activated serum (ZAS)-induced oedema in the skin, platelet-activating factor (PAF)-induced neutrophilia and interleukin-lf (IL-1J)-induced corticosterone (CCS) release.3 At the 4 h time-point of the zymosan inflamed air-pouch model, treatment with LCS3 did not modify the number of polymorphonuclear leucocytes (PMN) recruited: 7.84+ 1.01 and 7.00 + 0.77 x 106 PMN per mouse for NSS-and LCS3 group, n =7. However, several other parameters of cell activation including myeloperoxidase (MPO) and elastase activities were increased (2.2 fold, P<0.05, and 6.5 fold, P<0.05, respectively) in the lavage fluids of these mice. Similarly, a significant increase in the amount of immunoreactive prostaglandin E2 (PGE2; 1.81 fold, P<0.05) and IL-la (2.75 fold, P<0.05), but not tumour necrosis factor-a (TNF-a), was also observed in LCS3-treated mice. 4 The recruitment of PMN into the zymosan inflamed air-pouches by 24 h had declined substantially (4.13+0.61 x 106 PMN per mouse, n=12) in the NSS-treated mice, whereas high values were still measured in those treated with LCS3 (9.35+1.20x 106 PMN per mouse, n=12, P<0.05). A similar effect was also found following sub-chronic treatment of mice with LCPS1: 6.48 + 0.10 x 106 PMN per mouse, vs. 2.77 + 1.20 and 2.64 + 0.49 x 106 PMN per mouse for PBS-and NSS-treated groups (n = 7, P<0.05). Most markers of inflammation were also increased in the lavage fluids of LCS3-treated mice: MPO and elastase showed a 2.47 fold and 17 fold increase, respectively (P<0.05 in both cases); TNF-a showed a 11.1 fold increase (P< 0.05) whereas the IL-lIa levels were not significantly modified. PGE2 was still detectable in most (5 out of 7) of the mice treated with LCS3 but only in 2 out of 7 of the NSStreated mice. 5 Intradermal injection of 50% ZAS caused a significant increase in the 2 hoedema formation in the skin of LCS3-treated mice in comparison to PBS-and NSS-treated animals: 16.7 + 1.5

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The local anti‐inflammatory action of dexamethasone in the rat carrageenin oedema model is reversed by an antiserum to lipocortin 1

Cited by 46 publications

References 21 publications

Immunoneutralization of Lipocortin 1 Reverses the Acute Inhibitory Effects of Dexamethasone on the Hypothalamo-Pituitary-Adrenocortical Responses to Cytokines in the Rat in vitro and in vivo

Immunoneutralization of Lipocortin 1 Reverses the Acute Inhibitory Effects of Dexamethasone on the Hypothalamo-Pituitary-Adrenocortical Responses to Cytokines in the Rat in vitro and in vivo

Anti-inflammatory functions of glucocorticoid-induced genes

Acute inflammatory response in the mouse: exacerbation by immunoneutralization of lipocortin 1

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