Cytokine transcripts in pediatric tuberculosis: a study with bronchoalveolar cells.
Pediatric tuberculosis (TB) differs from adult TB in many features. To date, cytokine expression has not been studied in children with TB. The relative amounts of the various cytokines released at the site of infection may be important determinants of TB disease development and pathology. We determined cytokine transcripts in bronchoalveolar cells (BACs) recovered from 9 children presenting with TB and from 9 children with pulmonary diseases other than TB. An RT-PCR-based method was developed to quantify the mRNAs encoding six cytokines (IFN- gamma, IL-12, TNF- alpha, IL-10, IL-4, TGF- beta 1) known to play key roles in mycobacterial infections. Expression of mRNA encoding TGF- beta, TNF- alpha and IFN- gamma was statistically significantly higher in BACs from children with TB than in BACs from children with other pulmonary diseases; whereas the levels of mRNA transcription for TGF- beta is high, the levels of mRNA transcription for IFN- gamma and TNF- alpha remain low. All children had low levels of mRNA for IL-12(p40). IL-4 was barely detectable in all cases. Children with miliary TB had high levels of IL-10 transcripts and low levels of mRNA encoding TGF- beta. The immunosuppressive cytokines TGF- beta and IL-10, are overproduced in children with non-miliary TB and miliary TB respectively and are probably involved in the progression of the disease. These data suggest that Th1 responses are reduced in children with TB.
Aubert-Pivert
E M
EM
Unité de Génétique Mycobactérienne, Département de Physiopathologie, Institut Pasteur, 25 rue du Docteur Roux, 75728 Paris Cedex 15, France. epivert@pasteur.fr
Chedevergne
F M
FM
Lopez-Ramirez
G M
GM
Colle
J H
JH
Scheinmann
P L
PL
Gicquel
B M
BM
de Blic
J M
JM
D000293:Adolescent; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000032:analysis; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma