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Fluvastatin treatment inhibits leucocyte adhesion and extravasation in models of complement‐mediated acute inflammation
SUMMARY Complement activation plays a relevant role in the development of tissue damage under inflammatory conditions, and clinical and experimental observations emphasize its contribution to inflammatory vasculitides. Statins have recently been shown to reduce cardiovascular morbidity independently...
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| Published in: | Clinical and experimental immunology 2004-02, Vol.135 (2), p.186-193 |
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| cites | cdi_FETCH-LOGICAL-c6248-25db90256fc2d0efae02e6428d11736182c29276b43e00b90b38b4ef188829f03 |
| container_end_page | 193 |
| container_issue | 2 |
| container_start_page | 186 |
| container_title | Clinical and experimental immunology |
| container_volume | 135 |
| creator | FISCHETTI, F. CARRETTA, R. BOROTTO, G. DURIGUTTO, P. BULLA, R. MERONI, P. L. TEDESCO, F. |
| description | SUMMARY
Complement activation plays a relevant role in the development of tissue damage under inflammatory conditions, and clinical and experimental observations emphasize its contribution to inflammatory vasculitides. Statins have recently been shown to reduce cardiovascular morbidity independently of plasma cholesterol lowering and in vitro studies support a direct anti‐inflammatory action of these drugs. The aim of this study was to verify the in vivo effect of fluvastatin on complement‐mediated acute peritoneal inflammation. The effect of oral treatment with fluvastatin was investigated in normo‐cholesterolaemic rats that received intraperitoneal injection of either yeast‐activated rat serum (Y‐act RS) or lipopolysaccharide to induce peritoneal inflammation monitored by the number of PMN recruited in peritoneal fluid washes. In addition, vascular adherence and extravasation of leucocytes were evaluated by direct videomicroscopy examination on mesentery postcapillary venules topically exposed to Y‐act RS. The number of PMN in the peritoneal washes of rats treated with fluvastatin was 38% lower than that of untreated animals (P |
| doi_str_mv | 10.1111/j.1365-2249.2003.02358.x |
| format | article |
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Complement activation plays a relevant role in the development of tissue damage under inflammatory conditions, and clinical and experimental observations emphasize its contribution to inflammatory vasculitides. Statins have recently been shown to reduce cardiovascular morbidity independently of plasma cholesterol lowering and in vitro studies support a direct anti‐inflammatory action of these drugs. The aim of this study was to verify the in vivo effect of fluvastatin on complement‐mediated acute peritoneal inflammation. The effect of oral treatment with fluvastatin was investigated in normo‐cholesterolaemic rats that received intraperitoneal injection of either yeast‐activated rat serum (Y‐act RS) or lipopolysaccharide to induce peritoneal inflammation monitored by the number of PMN recruited in peritoneal fluid washes. In addition, vascular adherence and extravasation of leucocytes were evaluated by direct videomicroscopy examination on mesentery postcapillary venules topically exposed to Y‐act RS. The number of PMN in the peritoneal washes of rats treated with fluvastatin was 38% lower than that of untreated animals (P < 0·05) 12 h after LPS injection, and was even lower (56%) in rats treated with Y‐act RS already 8 h after injection (P < 0·02). Firm adhesion to endothelium and extravasation of leucocytes evaluated under direct videomicroscopy observation were significantly inhibited in fluvastatin treated rats (77% and 72%, respectively; P < 0·01), 120 min after treatment with Y‐act RS. Our results demonstrate that fluvastatin inhibits in vivo complement‐dependent acute peritoneal inflammation and suggest a role for statins in preventing the inflammatory flares usually associated with complement activation in chronic diseases, such as SLE or rheumatoid arthritis.</description><identifier>ISSN: 0009-9104</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1111/j.1365-2249.2003.02358.x</identifier><identifier>PMID: 14738444</identifier><identifier>CODEN: CEXIAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Administration, Oral ; Animal Studies ; Animals ; Anti-Inflammatory Agents - administration & dosage ; Biological and medical sciences ; Cell Adhesion - immunology ; Chemotaxis, Leukocyte - immunology ; complement ; Complement Activation - immunology ; Disease Models, Animal ; Endothelium, Vascular - immunology ; Fatty Acids, Monounsaturated - administration & dosage ; Fluvastatin ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Immunopathology ; Indoles - administration & dosage ; leucocytes ; Leukocytes - drug effects ; Leukocytes - immunology ; Lipids - blood ; Male ; Medical sciences ; Microscopy, Video - methods ; Neutrophils - immunology ; Peritoneal Cavity ; Peritonitis - immunology ; rat ; Rats ; Rats, Wistar ; videomicroscopy</subject><ispartof>Clinical and experimental immunology, 2004-02, Vol.135 (2), p.186-193</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. Feb 2004</rights><rights>2004 Blackwell Publishing Ltd 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6248-25db90256fc2d0efae02e6428d11736182c29276b43e00b90b38b4ef188829f03</citedby><cites>FETCH-LOGICAL-c6248-25db90256fc2d0efae02e6428d11736182c29276b43e00b90b38b4ef188829f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808935/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808935/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15518763$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14738444$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FISCHETTI, F.</creatorcontrib><creatorcontrib>CARRETTA, R.</creatorcontrib><creatorcontrib>BOROTTO, G.</creatorcontrib><creatorcontrib>DURIGUTTO, P.</creatorcontrib><creatorcontrib>BULLA, R.</creatorcontrib><creatorcontrib>MERONI, P. L.</creatorcontrib><creatorcontrib>TEDESCO, F.</creatorcontrib><title>Fluvastatin treatment inhibits leucocyte adhesion and extravasation in models of complement‐mediated acute inflammation</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>SUMMARY
Complement activation plays a relevant role in the development of tissue damage under inflammatory conditions, and clinical and experimental observations emphasize its contribution to inflammatory vasculitides. Statins have recently been shown to reduce cardiovascular morbidity independently of plasma cholesterol lowering and in vitro studies support a direct anti‐inflammatory action of these drugs. The aim of this study was to verify the in vivo effect of fluvastatin on complement‐mediated acute peritoneal inflammation. The effect of oral treatment with fluvastatin was investigated in normo‐cholesterolaemic rats that received intraperitoneal injection of either yeast‐activated rat serum (Y‐act RS) or lipopolysaccharide to induce peritoneal inflammation monitored by the number of PMN recruited in peritoneal fluid washes. In addition, vascular adherence and extravasation of leucocytes were evaluated by direct videomicroscopy examination on mesentery postcapillary venules topically exposed to Y‐act RS. The number of PMN in the peritoneal washes of rats treated with fluvastatin was 38% lower than that of untreated animals (P < 0·05) 12 h after LPS injection, and was even lower (56%) in rats treated with Y‐act RS already 8 h after injection (P < 0·02). Firm adhesion to endothelium and extravasation of leucocytes evaluated under direct videomicroscopy observation were significantly inhibited in fluvastatin treated rats (77% and 72%, respectively; P < 0·01), 120 min after treatment with Y‐act RS. Our results demonstrate that fluvastatin inhibits in vivo complement‐dependent acute peritoneal inflammation and suggest a role for statins in preventing the inflammatory flares usually associated with complement activation in chronic diseases, such as SLE or rheumatoid arthritis.</description><subject>Administration, Oral</subject><subject>Animal Studies</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - administration & dosage</subject><subject>Biological and medical sciences</subject><subject>Cell Adhesion - immunology</subject><subject>Chemotaxis, Leukocyte - immunology</subject><subject>complement</subject><subject>Complement Activation - immunology</subject><subject>Disease Models, Animal</subject><subject>Endothelium, Vascular - immunology</subject><subject>Fatty Acids, Monounsaturated - administration & dosage</subject><subject>Fluvastatin</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Immunopathology</subject><subject>Indoles - administration & dosage</subject><subject>leucocytes</subject><subject>Leukocytes - drug effects</subject><subject>Leukocytes - immunology</subject><subject>Lipids - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microscopy, Video - methods</subject><subject>Neutrophils - immunology</subject><subject>Peritoneal Cavity</subject><subject>Peritonitis - immunology</subject><subject>rat</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>videomicroscopy</subject><issn>0009-9104</issn><issn>1365-2249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNqNks1u1DAQxy0EosvCKyALCW4J_oi9zgEktGqhUiUucLYcZ8J65dhLnJTdG4_QZ-yT4HRXLXABX_wxv_9f45lBCFNS0rzebkvKpSgYq-qSEcJLwrhQ5f4RWtwHHqMFIaQuakqqM_QspW2-SinZU3RGqxVXVVUt0OHCT9cmjWZ0AY8DmLGHMGIXNq5xY8IeJhvtYQRs2g0kFwM2ocWwHweTdVmWX7K0jy34hGOHbex3HmaX2583PbTOjNBiY6fs4ULnTd_fqZ6jJ53xCV6c9iX6enH-Zf2puPr88XL94aqwklWqYKJtasKE7CxrCXQGCANZMdVSuuKSKmZZzVayqTgQktGGq6aCjiqlWN0RvkTvj767qcnp2JzYYLzeDa43w0FH4_SfkeA2-lu81lQRVXORDd6cDIb4fYI06t4lC96bAHFKWhFKaqHoP0FaM6lYLv0SvfoL3MZpCLkKmZFqJWoxQ-oI2SGmNEB3nzIlep4CvdVzs_XcbD1Pgb6bAr3P0pe_f_lBeGp7Bl6fAJOs8d1ggnXpgROCqpXkmXt35H44D4f_TkCvzy_nE_8FPcrRMw</recordid><startdate>200402</startdate><enddate>200402</enddate><creator>FISCHETTI, F.</creator><creator>CARRETTA, R.</creator><creator>BOROTTO, G.</creator><creator>DURIGUTTO, P.</creator><creator>BULLA, R.</creator><creator>MERONI, P. L.</creator><creator>TEDESCO, F.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Oxford University Press</general><general>Blackwell Science Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200402</creationdate><title>Fluvastatin treatment inhibits leucocyte adhesion and extravasation in models of complement‐mediated acute inflammation</title><author>FISCHETTI, F. ; CARRETTA, R. ; BOROTTO, G. ; DURIGUTTO, P. ; BULLA, R. ; MERONI, P. L. ; TEDESCO, F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6248-25db90256fc2d0efae02e6428d11736182c29276b43e00b90b38b4ef188829f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Administration, Oral</topic><topic>Animal Studies</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - administration & dosage</topic><topic>Biological and medical sciences</topic><topic>Cell Adhesion - immunology</topic><topic>Chemotaxis, Leukocyte - immunology</topic><topic>complement</topic><topic>Complement Activation - immunology</topic><topic>Disease Models, Animal</topic><topic>Endothelium, Vascular - immunology</topic><topic>Fatty Acids, Monounsaturated - administration & dosage</topic><topic>Fluvastatin</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Immunopathology</topic><topic>Indoles - administration & dosage</topic><topic>leucocytes</topic><topic>Leukocytes - drug effects</topic><topic>Leukocytes - immunology</topic><topic>Lipids - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microscopy, Video - methods</topic><topic>Neutrophils - immunology</topic><topic>Peritoneal Cavity</topic><topic>Peritonitis - immunology</topic><topic>rat</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>videomicroscopy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FISCHETTI, F.</creatorcontrib><creatorcontrib>CARRETTA, R.</creatorcontrib><creatorcontrib>BOROTTO, G.</creatorcontrib><creatorcontrib>DURIGUTTO, P.</creatorcontrib><creatorcontrib>BULLA, R.</creatorcontrib><creatorcontrib>MERONI, P. L.</creatorcontrib><creatorcontrib>TEDESCO, F.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FISCHETTI, F.</au><au>CARRETTA, R.</au><au>BOROTTO, G.</au><au>DURIGUTTO, P.</au><au>BULLA, R.</au><au>MERONI, P. L.</au><au>TEDESCO, F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fluvastatin treatment inhibits leucocyte adhesion and extravasation in models of complement‐mediated acute inflammation</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>2004-02</date><risdate>2004</risdate><volume>135</volume><issue>2</issue><spage>186</spage><epage>193</epage><pages>186-193</pages><issn>0009-9104</issn><eissn>1365-2249</eissn><coden>CEXIAL</coden><abstract>SUMMARY
Complement activation plays a relevant role in the development of tissue damage under inflammatory conditions, and clinical and experimental observations emphasize its contribution to inflammatory vasculitides. Statins have recently been shown to reduce cardiovascular morbidity independently of plasma cholesterol lowering and in vitro studies support a direct anti‐inflammatory action of these drugs. The aim of this study was to verify the in vivo effect of fluvastatin on complement‐mediated acute peritoneal inflammation. The effect of oral treatment with fluvastatin was investigated in normo‐cholesterolaemic rats that received intraperitoneal injection of either yeast‐activated rat serum (Y‐act RS) or lipopolysaccharide to induce peritoneal inflammation monitored by the number of PMN recruited in peritoneal fluid washes. In addition, vascular adherence and extravasation of leucocytes were evaluated by direct videomicroscopy examination on mesentery postcapillary venules topically exposed to Y‐act RS. The number of PMN in the peritoneal washes of rats treated with fluvastatin was 38% lower than that of untreated animals (P < 0·05) 12 h after LPS injection, and was even lower (56%) in rats treated with Y‐act RS already 8 h after injection (P < 0·02). Firm adhesion to endothelium and extravasation of leucocytes evaluated under direct videomicroscopy observation were significantly inhibited in fluvastatin treated rats (77% and 72%, respectively; P < 0·01), 120 min after treatment with Y‐act RS. Our results demonstrate that fluvastatin inhibits in vivo complement‐dependent acute peritoneal inflammation and suggest a role for statins in preventing the inflammatory flares usually associated with complement activation in chronic diseases, such as SLE or rheumatoid arthritis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>14738444</pmid><doi>10.1111/j.1365-2249.2003.02358.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Administration, Oral Animal Studies Animals Anti-Inflammatory Agents - administration & dosage Biological and medical sciences Cell Adhesion - immunology Chemotaxis, Leukocyte - immunology complement Complement Activation - immunology Disease Models, Animal Endothelium, Vascular - immunology Fatty Acids, Monounsaturated - administration & dosage Fluvastatin Fundamental and applied biological sciences. Psychology Fundamental immunology Immunopathology Indoles - administration & dosage leucocytes Leukocytes - drug effects Leukocytes - immunology Lipids - blood Male Medical sciences Microscopy, Video - methods Neutrophils - immunology Peritoneal Cavity Peritonitis - immunology rat Rats Rats, Wistar videomicroscopy |
| title | Fluvastatin treatment inhibits leucocyte adhesion and extravasation in models of complement‐mediated acute inflammation |
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