The Role of Interleukin-1 in Wound Biology. Part II

• DOI: 10.1213/ane.0b013e3181f691eb
• Publication Date: 2010-10-02T10:48:11Z
• 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
• Keywords: Keratinocytes; Male; 0301 basic medicine; Analgesics; Cesarean Section; Chemokine CXCL1; Dermatologic Surgical Procedures; Interleukin-1beta; Interleukin-8; Anti-Inflammatory Agents; Disease Models, Animal; Interleukin 1 Receptor Antagonist Protein; 03 medical and health sciences; Interleukin-1alpha; Animals; Humans; Female; Chemokines; Inflammation Mediators; Cells, Cultured; Chemokine CCL3; Interleukin-1

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.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.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.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.