Relationship between inflammatory mediator patterns and anemia in HIV-1 positive and exposed children with Plasmodium falciparum malaria
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Date
2012
Authors
Davenport, G. C.
Hittner, James B.
Were, T.
Ong'echa, J. M.
Perkins, D. J.
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley Periodicals, Inc.
Abstract
Anemia is the primary hematological manifestation of both Plasmodium falciparum malaria and HIV-1 in pediatric populations in sub-Saharan Africa. We have previously shown that HIV-1 positive and exposed children have greater risk of developing severe anemia (hemoglobin, Hb <6.0 g dL⁻¹) during acute malaria. However, enhanced severity of anemia was unrelated to either erythropoietic suppression or parasite-driven red blood cell hemolysis. To further explore mechanisms of anemia, circulating inflammatory mediators (IMs) were determined using a 25-plex bead array in P. falciparum-infected (Pf[+]) children (3-36 month, n = 194) stratified into three groups: HIV-1 negative (HIV-1[-]/Pf[+]); HIV-1 exposed (HIV-1[exp]/Pf[+]); and HIV-1 infected (HIV-1[+]/Pf[+]). IL-12, MIG/CXCL9, eotaxin/CCL11, and GM-CSF differed significantly and progressively increased across the groups (HIV-1[-] →HIV-1[exp] →HIV-1[+]). To further explore the relationship between the inflammatory milieu (i.e., cytokines, chemokines, and growth factors) and HIV-1 status, the large panel of IMs was reduced into discrete groups by principal component factor analysis. Of the six principal components that emerged, three components were significantly higher in the HIV-1 [+]/pf [+] and HIV [exp]/Pf [+] groups, demonstrating that inflammatory profiles differ according to HIV-1 status. Additional analyses exploring the relationship between the components and anemia revealed significant positive correlations between Hb and Component 3 (IL-1Ra, IL-7, IL-17, IFN-α, IFN-γ, MIG/CXCL9) in the HIV-1[-]/Pf [+] group, and Component 4 (IL-4, IL-5, IL-12, Eotaxin/CCL11) in HIV-1[+]/Pf [+] children. Further analyses of the HIV-1[+]/Pf [+] group revealed that IL-12 had the strongest association with anemia. Results presented here demonstrate that there are unique relationships between the inflammatory environment and anemia in HIV-1 positive and exposed children with malaria.
Description
doi: 10.1002/ajh.23200
Keywords
Citation
Wiley Periodicals, Inc. 87(7):652-8, July 2012