?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F9585%2F&rft.title=Impact+of+Hemozoin+on+Hematological+Outcomes+and+Innate+Inflammatory+Mediator+Production+in+Infants+and+Young+Children+with+Malarial+Anemia&rft.creator=Kristoff%2C+Jan&rft.description=Malaria+causes+300-500+million+clinical+cases+and+1-3+million+deaths+per+year%2C+the+majority+of+which+occur+in+young+African+children.+Ingestion+of+hemozoin+by+peripheral+blood+mononuclear+cells+(PBMC)+initiates+the+cytokine-mediated+cascade+of+immune+dysregulation+in+malaria.+Innate+immunity+plays+a+critical+role+in+protective+responses+against+infection%2C+which+are+determined+by+an+appropriate+balance+between+pro-+and+anti-inflammatory+mediators.+Pro-inflammatory+mediators+(TNF-%26%23945%2C+IL-12%2C+IFN-%26%23947)+that+control+parasitemia+also+contribute+to+pathology.+Over-production+of+immunomodulatory+cytokines+(TGF-%26%23946%2C+IL-10)+suppresses+the+protective+pro-inflammatory+immune+response.+The+effects+of+hemozoin+on+hematological+outcomes+and+inflammatory+mediator+production+in+children+with+malarial+anemia+and+the+temporal+kinetics+of+hemozoin-induced+cytokine+dysregulation+in+cultured+PBMC+were+investigated+in+this+study.+Hematological+analyses+of+healthy+control+(HC)%2C+uncomplicated+malaria+(UM)%2C+mild+malarial+anemia+(MlMA)%2C+moderate+malarial+anemia+(MdMA)%2C+and+severe+malarial+anemia+(SMA)+groups+revealed+that+age%2C+temperature%2C+and+all+erythrocyte%2C+leukocyte%2C+and+platelet+indices+were+significantly+different+between+clinical+categories.+Neither+parasitemia+nor+the+prevalence+of+high+density+parasitemia+(HDP)+differed+significantly+between+clinical+groups.+Stratification+of+study+participants+according+to+proportion+of+pigment-containing+monocytes+(PCM)+demonstrated+that+parasitemia%2C+HDP%2C+temperature%2C+and+most+leukocyte%2C+erythrocyte%2C+and+platelet+indices+were+significantly+different+between+0%25%2C+%26%238804+10%25%2C+and+%3E+10%25+PCM+categories.+The+%3E+10%25+PCM+category+contained+children+with+the+lowest+hemoglobin%2C+hematocrit%2C+and+erythrocyte+counts+and+the+greatest+proportion+of+children+with+SMA.+Plasma+IFN-%26%23945%2C+IL-4%2C+IL-6%2C+IL-10%2C+and+IL-12p40%2Fp70+levels+differed+significantly+between+clinical+categories+but+not+between+UM+and+SMA+groups.+Plasma+IFN-%26%23945%2C+IFN-%26%23947%2C+TNF-%26%23945%2C+IL-1%26%23946%2C+IL-2%2C+IL-4%2C+IL-6%2C+IL-10%2C+and+IL-12p40%2Fp70+were+not+significantly+associated+with+%25+PCM.+%26%23946-hematin-induced+IL-1%26%23946%2C+IL-2%2C+IL-6%2C+IL-12p35%2C+IL-12p40%2C+IL-18%2C+IFN-%26%23945%2C+IFN-%26%23947%2C+TNF-%26%23945%2C+LT-%26%23945%2C+NOS-2A%2C+COX-1%2C+COX-2%2C+IL-4%2C+IL-10%2C+and+TGF-%26%23946+expression+in+cultured+PBMC+revealed+a+pro-inflammatory+response+that+varied+in+magnitude+among+individuals.+Importantly%2C+innate+inflammatory+mediators+modulate+the+adaptive+immune+response+to+Plasmodium+parasites.+Of+public+health+significance%2C+a+better+understanding+of+the+molecular+mechanisms+governing+these+responses+will+facilitate+the+development+of+more+immunogenic+vaccines%2C+through+inclusion+of+cytokines+or+other+compounds+that+activate+the+innate+immune+system.&rft.date=2007-02-02&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F9585%2F1%2FKristoff%252812-1-06%2529.pdf&rft.identifier=++Kristoff%2C+Jan++(2007)+Impact+of+Hemozoin+on+Hematological+Outcomes+and+Innate+Inflammatory+Mediator+Production+in+Infants+and+Young+Children+with+Malarial+Anemia.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++