title: Multiplex determination of murine seminal fluid cytokine profiles.
abstract: Seminal fluid is known to be responsible for orchestrating mating-induced immunomodulation. Central to this process are numerous cytokines that modulate uterine leukocyte recruitment and trafficking. Despite this, a comprehensive analysis of the cytokine profile of murine seminal fluid is lacking. This study addressed this issue by using multiplex immunoassays to characterise the profile of interleukin (IL)-1alpha , IL-1beta , IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha , MIP-1beta , regulated upon activation normal T-cell expressed and secreted (RANTES), and tumour necrosis factor (TNF)-alpha in fluid drawn from the seminal vesicles of single mice (n = 18). Their levels and ratios were compared with those found in serum. IL-1alpha , IL-1beta , IL-2, IL-5, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-17, GM-CSF, IFN-gamma, MCP-1 and TNF-alpha levels were significantly higher in serum; IL-4, G-CSF, eotaxin, KC and RANTES exhibited the opposite trend. Based on these findings, we propose a model of mating-induced immunomodulation that implicates seminal eotaxin, RANTES and MIP-1alpha in the relocation and concentration of extravasated migrating endometrial eosinophils to the luminal epithelium. Furthermore, KC may participate in uterine neutrophil chemotaxis and activation. Eotaxin and MIP-alpha , together with IL-1beta and IL-9, may also enhance further cytokine synthesis for endometrial antigen-presenting cell recruitment for processing paternal ejaculate antigens. IL-4 and G-CSF could also minimise deleterious cell-mediated immunity and modulate IFN-gamma production, thereby supporting the establishment of pregnancy.
authors.affiliation: Perinatal Research Group, Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, Level 4, JIF Building, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: Nadia
authors.initials: N
authors.lastname: Gopichandran
authors.forename: Uma V
authors.initials: UV
authors.lastname: Ekbote
authors.forename: James J
authors.initials: JJ
authors.lastname: Walker
authors.forename: David
authors.initials: D
authors.lastname: Brooke
authors.forename: Nicolas M
authors.initials: NM
authors.lastname: Orsi
mesh_terms: D000818:Animals; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis / Q000097:blood; D018925:Chemokines / Q000032:analysis / Q000097:blood; D019742:Chemokines, CC / Q000032:analysis / Q000097:blood; D016207:Cytokines / Q000032:analysis / Q000097:blood; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis / Q000097:blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000097:blood; D007108:Immune Tolerance; D007118:Immunoassay / Q000379:methods; D007155:Immunologic Factors / Q000032:analysis* / Q000097:blood; D007378:Interleukins / Q000032:analysis / Q000097:blood; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012661:Semen / Q000276:immunology*
chemical_list: C515457:Ccl11 protein, mouse; C491768:Ccl2 protein, mouse; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D007155:Immunologic Factors; D007378:Interleukins; D019402:Macrophage Inflammatory Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor