title: Impaired pneumovax-23-induced monocyte-derived cytokine production in patients with common variable immunodeficiency.
abstract: BACKGROUND
  Streptococcus pneumoniae is one of the most common infectious pathogens in common variable immunodeficiency (CVID). Both innate and adaptive immune response appears to play a role in defense against S. pneumoniae. In mice, it has been established that TLR2 and macrophages-derived cytokines (IL-6, TNF-alpha) play a crucial role in defense against S. pneumoniae. In humans, monocyte/macrophage-derived cytokines in response to S. pneumoniae have not been studied. Patients with CVID respond poorly to Pneumovax-23 (containing all capsular polysaccharides) vaccination.
  
  
  RESULTS
  In this study, we show that Pneumovax-23, in a concentration and time-dependent manner, induced secretion of IL-6, IL-10, and TNF-alpha by monocytes and not by B cells or T cells from healthy controls. Furthermore, Pneumovax-23-induced secretion of IL-6 and TNF-alpha was significantly less in patients with CVID as compared with controls. In addition, Pneumovax-23-induced upregulation of TLR2 in all four subsets of monocytes; however, differences between control and CVID were not significant.
  
  
  CONCLUSIONS
  Pneumovax-23-induced monocytes-derived cytokine production is impaired in CVID, which may play an important role in increased susceptibility of CVID patients to S. pneumoniae infection.
authors.affiliation: Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Hong
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Agrawal
authors.forename: Sastry
authors.initials: S
authors.lastname: Gollapudi
authors.forename: Sudhir
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology; D001428:Bacterial Vaccines / Q000494:pharmacology*; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011008:Pneumococcal Infections / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2