CXCL6 (granulocyte chemotactic protein-2): a novel chemokine involved in the innate immune response of the amniotic cavity.
OBJECTIVE
CXCL6 is a potent pro-inflammatory neutrophil chemoattractant and activator whose activity during pregnancy is not well-established. The purpose of this study was to determine if CXCL6 is present in amniotic fluid (AF) and if CXCL6 concentrations in AF change with labor (pre-term and term) or intra-amniotic infection/inflammation (IAI).


METHODS
A cross-sectional study was designed including the following groups: (1) mid-trimester (n = 65); (2) term no labor (n = 20); (3) term labor (n = 44); (4) patients with pre-term labor (PTL) with subsequent term delivery (n = 57); (5) PTL without IAI who delivered pre-term (n = 47); and (6) PTL with IAI (n = 62). AF CXCL6 concentrations were determined by ELISA.


RESULTS
CXCL6 was present in all term samples, but undetectable in 64/65 mid-trimester specimens. Patients with PTL and IAI had a significantly higher median AF CXCL6 concentration than those with PTL without IAI [228.9 pg/mL (0.0-8344.8) versus 55.7 pg/mL (0-454.4); P < 0.05] and those with PTL and term delivery [41.5 pg/mL (0-279.0); P < 0.05]. The median AF CXCL6 concentration did not change with spontaneous term labor [term no labor: 81.1 pg/mL (8.5-201.7) versus term labor: 75.2 pg/mL (6.7-378.7): P = 0.7].


CONCLUSIONS
(1) CXCL6 is detectable in AF and its concentration increases with gestational age; (2) IAI results in increased AF CXCL6 concentrations, suggesting that CXCL6 plays a role in the deployment of an inflammatory response; (3) In contrast to related chemokines, specifically IL-8, AF CXCL6 does not appear to be involved in spontaneous term parturition. These observations are novel, and suggest a role for CXCL6 in the innate immune response to microbial invasion of the amniotic cavity.
Mittal
Pooja
P
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA. prbchiefstaff@med.wayne.edu
Romero
Roberto
R
Kusanovic
Juan Pedro
JP
Edwin
Samuel S
SS
Gotsch
Francesca
F
Mazaki-Tovi
Shali
S
Espinoza
Jimmy
J
Erez
Offer
O
Nhan-Chang
Chia-Ling
CL
Than
Nandor G
NG
Vaisbuch
Edi
E
Hassan
Sonia S
SS
D000293:Adolescent; D000328:Adult; D000650:Amnion / Q000276:immunology* / Q000378:metabolism; D000653:Amniotic Fluid / Q000737:chemistry*; D054427:Chemokine CXCL6 / Q000032:analysis* / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D007113:Immunity, Innate; D007752:Obstetric Labor, Premature / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D047929:Term Birth / Q000276:immunology* / Q000378:metabolism
D054427:Chemokine CXCL6
Am J Obstet Gynecol. 2001 Sep;185(3):586-92
11568782
Biochemistry. 1993 Sep 28;32(38):10170-7
8399143
Dev Med Child Neurol. 1993 Jun;35(6):553-8
8504899
Fertil Steril. 1999 Jun;71(6):983-93
10360897
Semin Fetal Neonatal Med. 2004 Dec;9(6):437-44
15691781
Am J Reprod Immunol. 1992 Apr-May;27(3-4):117-23
1418402
Eur J Biochem. 1997 Feb 1;243(3):762-9
9057843
BJOG. 2005 Mar;112 Suppl 1:16-8
15715588
Am J Obstet Gynecol. 1993 Nov;169(5):1299-303
8238198
Am J Reprod Immunol. 1996 Jan;35(1):23-9
8789556
Hum Reprod. 1998 Apr;13(4):1036-43
9619567
Nat Med. 2000 May;6(5):589-93
10802718
J Immunol. 1997 Jun 1;158(11):5257-66
9164944
Am J Obstet Gynecol. 1989 Aug;161(2):336-41
2764054
Am J Obstet Gynecol. 2006 Sep;195(3):778-86
16949412
Paediatr Perinat Epidemiol. 2001 Jul;15 Suppl 2:41-56
11520399
Am J Obstet Gynecol. 1998 Mar;178(3):428-32
9539502
Fertil Steril. 2003 Jan;79(1):146-50
12524079
Blood. 1999 Jan 15;93(2):694-702
9885232
J Leukoc Biol. 1995 Jan;57(1):180-7
7829970
Mol Hum Reprod. 2000 Apr;6(4):375-81
10729321
J Biol Chem. 1995 Nov 10;270(45):27348-57
7592998
J Allergy Clin Immunol. 2003 Sep;112(3):556-62
13679815
Am J Obstet Gynecol. 1994 Dec;171(6):1660-7
7802084
Biochemistry. 1997 Mar 4;36(9):2716-23
9054580
Am J Obstet Gynecol. 1998 Jul;179(1):186-93
9704786
Acta Obstet Gynecol Scand. 2005 Jun;84(6):516-25
15901257
J Leukoc Biol. 1997 Nov;62(5):563-9
9365109
Am J Obstet Gynecol. 1992 May;166(5):1515-28
1595807
Am J Reprod Immunol. 1993 Sep-Oct;30(2-3):167-83
8311926
Am J Pathol. 2003 Nov;163(5):2103-11
14578208
Ann N Y Acad Sci. 2001 Sep;943:225-34
11594542
Hum Reprod. 2000 Apr;15(4):778-84
10739819
Hum Reprod. 1994 Feb;9(2):253-8
8027281
J Immunol. 1993 Feb 1;150(3):1000-10
8423327
Semin Reprod Med. 2007 Jan;25(1):21-39
17205421
Cytokine. 1993 Jan;5(1):81-8
7683506
Hum Reprod Update. 1995 Jul;1(4):385-96
9080214
Br J Cancer. 2006 Jun 19;94(12):1936-41
16721367
Acta Obstet Gynecol Scand. 2001 Sep;80(9):840-8
11531636
BJOG. 2006 Dec;113 Suppl 3:17-42
17206962
J Soc Gynecol Investig. 2005 Apr;12(3):145-55
15784499
Exp Cell Res. 2005 Feb 15;303(2):331-42
15652347
Eur J Immunol. 2004 Jul;34(7):1992-2000
15214047
Eur J Obstet Gynecol Reprod Biol. 1997 Jul;74(1):89-92
9243210
Fertil Steril. 2004 Oct;82(4):799-804
15482749
J Matern Fetal Neonatal Med. 2003 Jan;13(1):2-21
12710851
Placenta. 2007 Nov-Dec;28(11-12):1099-106
17664005
Acta Obstet Gynecol Scand. 2002 Oct;81(10):938-42
12366484
J Leukoc Biol. 1995 May;57(5):752-62
7539029
Am J Obstet Gynecol. 2006 Aug;195(2):394.e1-24
16890549
Acta Obstet Gynecol Scand. 2005 Aug;84(8):734-42
16026397
Obstet Gynecol. 1995 Aug;86(2):223-9
7617353
Immunity. 2000 Feb;12(2):121-7
10714678
Immunology. 1988 Sep;65(1):129-34
3181993
Ment Retard Dev Disabil Res Rev. 2002;8(1):3-13
11921380
Am J Obstet Gynecol. 2002 Jul;187(1):137-44
12114901
J Immunol. 1994 Dec 15;153(12):5682-8
7527448
J Perinat Med. 2004;32(5):391-9
15493713
Clin Exp Immunol. 2004 Oct;138(1):151-7
15373918
Ciba Found Symp. 1992;167:205-20; discussion 220-3
1425014
Placenta. 2003 Apr;24 Suppl A:S33-46
12842412
Placenta. 1991 May-Jun;12(3):285-8
1754577
J Clin Invest. 1990 May;85(5):1392-400
2332497
Am J Obstet Gynecol. 2006 Dec;195(6):1533-7
16796981
Reprod Biol Endocrinol. 2005 Aug 25;3:39
16122384
J Matern Fetal Neonatal Med. 2007 Jan;20(1):15-22
17437194
Obstet Gynecol. 1993 Jun;81(6):941-8
8497360
Am J Perinatol. 2000;17(7):357-65
12141522
Am J Obstet Gynecol. 1989 Sep;161(3):817-24
2675611
N Engl J Med. 2000 May 18;342(20):1500-7
10816189
Early Hum Dev. 2005 Jun;81(6):489-96
15935926
Am J Obstet Gynecol. 2001 Nov;185(5):1130-6
11717646
Am J Obstet Gynecol. 1995 Mar;172(3):960-70
7892891
Am J Obstet Gynecol. 1993 Oct;169(4):805-16
7694461
Acta Obstet Gynecol Scand. 2005 Dec;84(12):1141-4
16305697
Lab Invest. 2003 Jan;83(1):23-34
12533683
Clin Perinatol. 1995 Jun;22(2):281-342
7671540
Obstet Gynecol. 1996 Jan;87(1):94-8
8532275
Eur J Biochem. 1998 Jul 1;255(1):67-73
9692902
Nutr Rev. 2002 May;60(5 Pt 2):S19-25
12035853
Acta Obstet Gynecol Scand. 2003 May;82(5):423-31
12752072
Trends Endocrinol Metab. 2004 Dec;15(10):479-87
15541647
Eur J Immunol. 1998 Jan;28(1):164-70
9485196
Arch Surg. 1999 Dec;134(12):1360-6
10593335
Genomics. 1998 Jan 1;47(1):136-9
9465307
Acta Endocrinol (Copenh). 1993 Sep;129(3):220-4
8212986
Trends Immunol. 2004 Apr;25(4):201-9
15039047
Nat Immunol. 2001 Feb;2(2):108-15
11175802
Am J Obstet Gynecol. 1996 Oct;175(4 Pt 1):830-3
8885730
J Immunol. 2004 Aug 15;173(4):2231-5
15294933
Am J Obstet Gynecol. 1992 May;166(5):1382-8
1595794
Eur J Obstet Gynecol Reprod Biol. 2001 Feb;94(2):224-9
11165729
Clin Exp Allergy. 2006 Jun;36(6):748-59
16776676
Cytokine Growth Factor Rev. 1998 Sep-Dec;9(3-4):287-96
9918126
Am J Obstet Gynecol. 1991 Oct;165(4 Pt 1):813-20
1951537
Am J Reprod Immunol. 1994 Sep;32(2):108-13
7826499
Reproduction. 2005 Nov;130(5):569-81
16264088