Therapeutic evaluation of immunomodulators in reducing surgical wound infection.
Pseudomonas aeruginosa
CCL3 (MIP-1α)
fMLP (fMLF)
immunomodulators
innate immune system
leukocytes
lipopolysaccharides (LPS)
neutrophils
surgical site infection (SSI)
wound healing
wound infection
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
10
11
2021
received:
21
06
2021
accepted:
23
11
2021
entrez:
15
12
2021
pubmed:
16
12
2021
medline:
12
1
2022
Statut:
ppublish
Résumé
Despite many advances in infection control practices, including prophylactic antibiotics, surgical site infections (SSIs) remain a significant cause of morbidity, prolonged hospitalization, and death worldwide. Our innate immune system possesses a multitude of powerful antimicrobial strategies which make it highly effective in combating bacterial, fungal, and viral infections. However, pathogens use various stealth mechanisms to avoid the innate immune system, which in turn buy them time to colonize wounds and damage tissues at surgical sites. We hypothesized that immunomodulators that can jumpstart and activate innate immune responses at surgical sites, would likely reduce infection at surgical sites. We used three immunomodulators; fMLP (formyl-Methionine-Lysine-Proline), CCL3 (MIP-1α), and LPS (Lipopolysaccharide), based on their documented ability to elicit strong inflammatory responses; in a surgical wound infection model with Pseudomonas aeruginosa to evaluate our hypothesis. Our data indicate that one-time topical treatment with these immunomodulators at low doses significantly increased proinflammatory responses in infected and uninfected surgical wounds and were as effective, (or even better), than a potent prophylactic antibiotic (Tobramycin) in reducing P. aeruginosa infection in wounds. Our data further show that immunomodulators did not have adverse effects on tissue repair and wound healing processes. Rather, they enhanced healing in both infected and uninfected wounds. Collectively, our data demonstrate that harnessing the power of the innate immune system by immunomodulators can significantly boost infection control and potentially stimulate healing. We propose that topical treatment with these immunomodulators at the time of surgery may have therapeutic potential in combating SSI, alone or in combination with prophylactic antibiotics.
Identifiants
pubmed: 34907595
doi: 10.1096/fj.202101019R
pmc: PMC9058973
mid: NIHMS1801070
doi:
Substances chimiques
Immunologic Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22090Subventions
Organisme : NIAID NIH HHS
ID : R01 AI150668
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107713
Pays : United States
Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
Références
Nat Rev Immunol. 2016 May 27;16(6):378-91
pubmed: 27231052
Diabet Med. 2006 Jun;23(6):594-608
pubmed: 16759300
Infect Control Hosp Epidemiol. 2012 Mar;33(3):283-91
pubmed: 22314066
Nat Rev Mol Cell Biol. 2008 Aug;9(8):628-38
pubmed: 18628784
Clin Infect Dis. 2002 Mar 15;34(6):730-51
pubmed: 11850858
J Pediatr Orthop. 2013 Jul-Aug;33(5):479-87
pubmed: 23752143
Am J Respir Crit Care Med. 2014 Apr 1;189(7):799-811
pubmed: 24555512
Hum Gene Ther. 2004 Jan;15(1):21-34
pubmed: 14965375
J Immunol. 2013 Feb 15;190(4):1746-57
pubmed: 23319733
Expert Rev Mol Med. 2011 Jul 11;13:e23
pubmed: 21740602
N Engl J Med. 2000 Jan 20;342(3):161-7
pubmed: 10639541
J Leukoc Biol. 2005 May;77(5):598-625
pubmed: 15689384
Clin Infect Dis. 2004 Jun 15;38(12):1706-15
pubmed: 15227616
J Int Med Res. 2009 Sep-Oct;37(5):1528-42
pubmed: 19930861
Trends Mol Med. 2016 Jun;22(6):458-478
pubmed: 27178527
J Infect Dis. 2002 Nov 15;186(10):1522-5
pubmed: 12404174
FASEB J. 2010 Jul;24(7):2178-90
pubmed: 20181940
Int J Low Extrem Wounds. 2004 Dec;3(4):201-8
pubmed: 15866816
Biotechnol Lett. 2005 Sep;27(18):1337-47
pubmed: 16215847
Cell. 2010 Mar 19;140(6):821-32
pubmed: 20303873
Antimicrob Agents Chemother. 1999 Dec;43(12):2877-80
pubmed: 10582875
Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):303-8
pubmed: 22087006
Front Biosci. 2004 Jan 01;9:283-9
pubmed: 14766366
Cell. 2010 Mar 19;140(6):805-20
pubmed: 20303872
J Infect Dis. 2013 Apr;207(7):1105-14
pubmed: 23300163
Blood. 1996 Jul 15;88(2):690-6
pubmed: 8695817
Br J Surg. 2017 Jan;104(2):e55-e64
pubmed: 28121042
Annu Rev Immunol. 2009;27:229-65
pubmed: 19302040
Immunol Rev. 2016 Sep;273(1):76-93
pubmed: 27558329
Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15605-10
pubmed: 17030800
J Immunol. 2003 May 15;170(10):5268-75
pubmed: 12734376
Cell Host Microbe. 2010 Jul 22;8(1):7-11
pubmed: 20638636
Curr Biol. 2000 Jul 13;10(14):831-8
pubmed: 10899000
Nat Commun. 2016 Jan 26;7:10410
pubmed: 26811868
PLoS One. 2010 Mar 24;5(3):e9836
pubmed: 20352091
J Leukoc Biol. 2008 Jan;83(1):64-70
pubmed: 17884993
Dev Cell. 2017 Jun 19;41(6):674-684.e5
pubmed: 28633020
Nat Rev Mol Cell Biol. 2006 Aug;7(8):601-11
pubmed: 16936700
N Engl J Med. 1999 Sep 2;341(10):738-46
pubmed: 10471461
Immunity. 2006 Jan;24(1):79-91
pubmed: 16413925
Pathog Dis. 2018 Feb 1;76(1):
pubmed: 29325116
Science. 1987 Jun 5;236(4806):1229-37
pubmed: 3296190
Front Cell Infect Microbiol. 2016 Apr 05;6:39
pubmed: 27092298
J Clin Periodontol. 2005;32 Suppl 6:57-71
pubmed: 16128830
Nature. 1989 Feb 2;337(6206):471-3
pubmed: 2464767
Sci Rep. 2012;2:786
pubmed: 23139859
J Immunol. 2000 Nov 15;165(10):5392-6
pubmed: 11067888
Clin Orthop Relat Res. 2012 Oct;470(10):2690-4
pubmed: 22302655
Annu Rev Immunol. 2002;20:197-216
pubmed: 11861602
J Biol Chem. 2003 May 2;278(18):15587-94
pubmed: 12594207
J Hosp Infect. 2000 Jul;45(3):173-84
pubmed: 10896795
JAMA Surg. 2017 Aug 01;152(8):784-791
pubmed: 28467526
Eur Cell Mater. 2021 Aug 26;42:122-138
pubmed: 34435345
J Immunol. 1995 Jan 1;154(1):308-17
pubmed: 7995950
Surg Infect (Larchmt). 2013 Feb;14(1):73-156
pubmed: 23461695
Clin Exp Immunol. 2006 Jan;143(1):70-7
pubmed: 16367936
Infect Immun. 2009 Nov;77(11):4690-5
pubmed: 19703980
J Orthop Trauma. 2012 Jan;26(1):37-42
pubmed: 21804414
J Immunol. 2015 Aug 15;195(4):1341-9
pubmed: 26254266
J Biol Chem. 2015 Nov 27;290(48):29063-73
pubmed: 26451042
Science. 2004 Mar 5;303(5663):1532-5
pubmed: 15001782
Infect Control Hosp Epidemiol. 2014 Sep;35 Suppl 2:S66-88
pubmed: 25376070
Thromb Haemost. 2004 Aug;92(2):275-80
pubmed: 15269822
Front Plant Sci. 2015 Apr 08;6:219
pubmed: 25904927
J Invest Dermatol. 2022 Mar;142(3 Pt A):692-704.e14
pubmed: 34517005
JAMA Intern Med. 2013 Dec 9-23;173(22):2039-46
pubmed: 23999949
Immunity. 2011 May 27;34(5):637-50
pubmed: 21616434
Mol Pharmacol. 2013 Feb;83(2):389-98
pubmed: 23160941
Intern Med J. 2011 Jun;41(6):441-9
pubmed: 21309997
Cell. 2016 Dec 1;167(6):1469-1480.e12
pubmed: 27912057
Wound Repair Regen. 2015 Jul-Aug;23(4):557-64
pubmed: 25912785
Nat Immunol. 2005 Dec;6(12):1182-90
pubmed: 16369557
PLoS One. 2014 Mar 11;9(3):e91574
pubmed: 24618995
Clin Infect Dis. 2001 Sep 1;33 Suppl 2:S69-77
pubmed: 11486302
Immunity. 2010 Aug 27;33(2):266-78
pubmed: 20727790
Expert Opin Pharmacother. 2012 Mar;13(4):565-71
pubmed: 22292783
J Interferon Cytokine Res. 2015 Aug;35(8):585-99
pubmed: 25803788
Lancet Infect Dis. 2016 Dec;16(12):e288-e303
pubmed: 27816414
Antimicrob Agents Chemother. 1995 Nov;39(11):2423-5
pubmed: 8585720
PLoS One. 2015 Aug 05;10(8):e0134852
pubmed: 26244880
J Am Coll Surg. 2017 Jan;224(1):59-74
pubmed: 27915053
Nat Med. 2015 Jul;21(7):677-87
pubmed: 26121197
Anesth Analg. 2015 Jun;120(6):1289-96
pubmed: 25695673
Reg Anesth Pain Med. 2018 Oct;43(7):795-804
pubmed: 29905629
Clin Dermatol. 2007 Jan-Feb;25(1):19-25
pubmed: 17276197
Int J Artif Organs. 2005 Nov;28(11):1091-100
pubmed: 16353115
Genome Med. 2016 Apr 13;8(1):39
pubmed: 27074706
J Med Microbiol. 2016 Aug;65(8):738-744
pubmed: 27302326
Eur Respir J. 2002 Sep;20(3):658-64
pubmed: 12358344
J Bone Joint Surg Am. 2013 May 1;95(9):775-82
pubmed: 23636183
Sci Transl Med. 2016 Jun 15;8(343):343ra81
pubmed: 27306663
Am J Sports Med. 2014 Apr;42(4):973-8
pubmed: 24518877
J Infect Dis. 1988 Jul;158(1):13-22
pubmed: 3134490
Yonsei Med J. 2016 Jan;57(1):5-14
pubmed: 26632377
Infect Control Hosp Epidemiol. 1999 Nov;20(11):725-30
pubmed: 10580621
Nature. 2011 Oct 16;479(7371):117-21
pubmed: 22002608
J Am Acad Dermatol. 1990 Nov;23(5 Pt 1):903-12
pubmed: 2254475
Sci Rep. 2017 Oct 23;7(1):13829
pubmed: 29062042
Public Health Rep. 2007 Mar-Apr;122(2):160-6
pubmed: 17357358
Science. 1997 Apr 4;276(5309):75-81
pubmed: 9082989
PLoS One. 2009 Dec 15;4(12):e8305
pubmed: 20016850
Immunopharmacol Immunotoxicol. 1999 Aug;21(3):397-419
pubmed: 10466071
J Invest Dermatol. 2008 Jul;128(7):1812-20
pubmed: 18185533
Transplantation. 2018 Jan;102(1):21-34
pubmed: 28614192
Arch Surg. 1987 Feb;122(2):239-51
pubmed: 3492987
Antimicrob Agents Chemother. 2013 Nov;57(11):5559-64
pubmed: 23979752
Surg Infect (Larchmt). 2015 Feb;16(1):14-23
pubmed: 25761076
Annu Rev Immunol. 2015;33:257-90
pubmed: 25581309
Lancet Infect Dis. 2009 Nov;9(11):688-98
pubmed: 19850227
Am J Infect Control. 1999 Apr;27(2):97-132; quiz 133-4; discussion 96
pubmed: 10196487
Am J Infect Control. 2013 May;41(5 Suppl):S49-55
pubmed: 23622749
Scand J Infect Dis. 1974;6(4):333-7
pubmed: 4217466
FASEB J. 2018 Jul;32(7):3614-3622
pubmed: 29405096
Clin Infect Dis. 2003 Mar 1;36(5):592-8
pubmed: 12594640
Infect Control Hosp Epidemiol. 2011 Dec;32(12):1179-86
pubmed: 22080656
Wound Repair Regen. 2008 Jan-Feb;16(1):2-10
pubmed: 18211573
Nat Rev Immunol. 2008 Dec;8(12):911-22
pubmed: 18989317
PLoS Pathog. 2015 May 28;11(5):e1004934
pubmed: 26020630