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: 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
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 111 Issue 6 Pg. 1534-42 (Dec 2010) ISSN: 1526-7598 [Electronic] United States
• PMID: 20889944 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Anti-Inflammatory Agents
• CXCL1 protein, human
• Ccl3 protein, mouse
• Chemokine CCL3
• Chemokine CXCL1
• Chemokines
• Inflammation Mediators
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1
• Interleukin-1alpha
• Interleukin-1beta
• Interleukin-8
• keratinocyte-derived chemokines

Topics

• Analgesics (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cells, Cultured
• Cesarean Section
• Chemokine CCL3 (metabolism)
• Chemokine CXCL1 (metabolism)
• Chemokines (metabolism)
• Dermatologic Surgical Procedures
• 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)
• Sunburn (immunology)
• Time Factors
• Translational Research, Biomedical
• Wound Healing (drug effects)