title: The role of interleukin-1 in wound biology. Part II: In vivo and human translational studies.
abstract: 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.affiliation: Department of Anesthesia, Stanford University, Stanford, USA.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Hu
authors.forename: Deyong
authors.initials: D
authors.lastname: Liang
authors.forename: Xiangqi
authors.initials: X
authors.lastname: Li
authors.forename: Hong-Hsing
authors.initials: HH
authors.lastname: Liu
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: David
authors.initials: D
authors.lastname: Dill
authors.forename: Xiaoyou
authors.initials: X
authors.lastname: Shi
authors.forename: Yanli
authors.initials: Y
authors.lastname: Qiao
authors.forename: David
authors.initials: D
authors.lastname: Yeomans
authors.forename: Brendan
authors.initials: B
authors.lastname: Carvalho
authors.forename: Martin S
authors.initials: MS
authors.lastname: Angst
authors.forename: J David
authors.initials: JD
authors.lastname: Clark
authors.forename: Gary
authors.initials: G
authors.lastname: Peltz
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D002585:Cesarean Section; D054405:Chemokine CCL3 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D062109:Dermatologic Surgical Procedures; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010149:Postoperative Pain / Q000276:immunology / Q000517:prevention & control; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D013471:Sunburn / Q000276:immunology; D013997:Time Factors; D057170:Translational Research, Biomedical; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; C475829:CXCL1 protein, human; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D054360:Chemokine CXCL1; D018925:Chemokines; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D016209:Interleukin-8; C074302:keratinocyte-derived chemokines