title: The effects of vitamin A supplementation with measles vaccine on leucocyte counts and in vitro cytokine production.
abstract: As WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VAS v. placebo with MV, analysing leucocyte counts, whole blood in vitro cytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP ≥ 5 mg/l (28 v. 12%; P=0·005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-γ responses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3·97; 95% CI 1·44, 10·90) but not in males (GMR 0·44; 95% CI 0·14, 1·42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS.
authors.affiliation: 1Bandim Health Project,INDEPTH Network,Apartado 861,Bissau Codex 1004,Bissau,Guinea-Bissau.
authors.forename: Kristoffer Jarlov
authors.identifier: http://orcid.org/0000-0001-9687-5706
authors.initials: KJ
authors.lastname: Jensen
authors.affiliation: 1Bandim Health Project,INDEPTH Network,Apartado 861,Bissau Codex 1004,Bissau,Guinea-Bissau.
authors.forename: Ane Bærent
authors.initials: AB
authors.lastname: Fisker
authors.affiliation: 2Research Center for Vitamins and Vaccines,Bandim Health Project,Statens Serum Institut,Artillerivej 5,DK-2300 Copenhagen S,Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Andersen
authors.affiliation: 4Leiden University Medical Center,Gebouw 1,Kamer P4-25a,Postbus 9600,2300 RC Leiden,The Netherlands.
authors.forename: Erliyani
authors.initials: E
authors.lastname: Sartono
authors.affiliation: 4Leiden University Medical Center,Gebouw 1,Kamer P4-25a,Postbus 9600,2300 RC Leiden,The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Yazdanbakhsh
authors.affiliation: 1Bandim Health Project,INDEPTH Network,Apartado 861,Bissau Codex 1004,Bissau,Guinea-Bissau.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: 5Department of Clinical Immunology,Aarhus University Hospital,Palle Juul-Jensens Boulevard 99,DK-8200 Aarhus,Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Erikstrup
authors.affiliation: 1Bandim Health Project,INDEPTH Network,Apartado 861,Bissau Codex 1004,Bissau,Guinea-Bissau.
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006169:Guinea-Bissau / Q000453:epidemiology; D006801:Humans; D064789:Immunity, Heterologous; D007223:Infant; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D059012:Lost to Follow-Up; D008297:Male; D008457:Measles / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008458:Measles Vaccine / Q000009:adverse effects / Q000627:therapeutic use*; D009752:Nutritional Status; D015995:Prevalence; D012727:Sex Characteristics; D014801:Vitamin A / Q000009:adverse effects / Q000627:therapeutic use*; D014802:Vitamin A Deficiency / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008458:Measles Vaccine; D014801:Vitamin A
keywords: CRP C-reactive protein; Cytokines; Differential count; GMR geometric mean ratio; Heterologous immunity; Inflammation; MV measles vaccine; PHA phytohaemagglutinin; PR proportion ratio; Paediatric nutrition; RBP retinol-binding protein; VAD vitamin A deficiency; VAS vitamin A supplementation; Vitamin A supplementation