Document Detail


The role of interleukin-1 in wound biology. Part II: In vivo and human translational studies.
MedLine Citation:
PMID:  20889944     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In the accompanying paper, we demonstrate that genetic variation within Nalp1 could contribute to interstrain differences in wound chemokine production through altering the amount of interleukin (IL)-1 produced. We further investigate the role of IL-1 in incisional wound biology and its effect on wound chemokine production in vivo and whether this mechanism could be active in human subjects.
METHODS: A well-characterized murine model of incisional wounding was used to assess the in vivo role of IL-1 in wound biology. The amount of 7 different cytokines/chemokines produced within an experimentally induced skin incision on a mouse paw and the nociceptive response was analyzed in mice treated with an IL-1 inhibitor. We also investigated whether human IL-1β or IL-1α stimulated the production of chemokines by primary human keratinocytes in vitro, and whether there was a correlation between IL-1β and chemokine levels in 2 experimental human wound paradigms.
RESULTS: Administration of an IL-1 receptor antagonist to mice decreased the nociceptive response to an incisional wound, and reduced the production of multiple inflammatory mediators, including keratinocyte-derived chemokine (KC) and macrophage inhibitory protein (MIP)-1α, within the wounds. IL-1α and IL-1β stimulated IL-8 and GRO-α (human homologues of murine keratinocyte-derived chemokine) production by primary human keratinocytes in vitro. IL-1β levels were highly correlated with IL-8 in human surgical wounds, and at cutaneous sites of human ultraviolet B-induced sunburn injury.
CONCLUSIONS: IL-1 plays a major role in regulating inflammatory mediator production in wounds through a novel mechanism; by stimulating the production of multiple cytokines and chemokines, it impacts clinically important aspects of wound biology. These data suggest that administration of an IL-1 receptor antagonist within the perioperative period could decrease postsurgical wound pain.
Authors:
Yajing Hu; Deyong Liang; Xiangqi Li; Hong-Hsing Liu; Xun Zhang; Ming Zheng; David Dill; Xiaoyou Shi; Yanli Qiao; David Yeomans; Brendan Carvalho; Martin S Angst; J David Clark; Gary Peltz
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Publication Detail:
Type:  Journal Article     Date:  2010-10-01
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  111     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-25     Completed Date:  2011-01-07     Revised Date:  2011-03-29    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1534-42     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesia, Stanford University, Stanford, USA.
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MeSH Terms
Descriptor/Qualifier:
Analgesics / pharmacology
Animals
Anti-Inflammatory Agents / pharmacology
Cells, Cultured
Cesarean Section
Chemokine CCL3 / metabolism
Chemokine CXCL1 / metabolism
Chemokines / metabolism*
Disease Models, Animal
Female
Humans
Inflammation Mediators / metabolism*
Interleukin 1 Receptor Antagonist Protein / pharmacology
Interleukin-1 / metabolism*
Interleukin-1alpha / metabolism
Interleukin-1beta / metabolism
Interleukin-8 / metabolism
Keratinocytes / drug effects,  immunology*,  radiation effects
Male
Mice
Mice, Inbred C57BL
Pain, Postoperative / immunology,  prevention & control
Pregnancy
Randomized Controlled Trials as Topic
Skin / drug effects,  immunology,  radiation effects,  surgery*
Sunburn / immunology
Time Factors
Translational Research
Wound Healing* / drug effects
Grant Support
ID/Acronym/Agency:
R01 GM079126-04/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Analgesics; 0/Anti-Inflammatory Agents; 0/CXCL1 protein, human; 0/Ccl3 protein, mouse; 0/Chemokine CCL3; 0/Chemokine CXCL1; 0/Chemokines; 0/Inflammation Mediators; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1; 0/Interleukin-1alpha; 0/Interleukin-1beta; 0/Interleukin-8; 147037-79-4/keratinocyte-derived chemokines
Comments/Corrections
Comment In:
Anesth Analg. 2010 Dec;111(6):1335-6   [PMID:  21106965 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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