Expression of gamma-IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients.
Various cytokines are upregulated in acute allograft rejection (AR). Local production of Th-1 cytokines is suggested to play a pathogenic role in AR, and Th-2 cytokines in the development of allograft tolerance. The purpose of this study was to correlate the expression of Th-1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN)], and Th-2 [interleukin-10 (IL-10)] cytokines in bronchoalveolar lavage (BAL) fluid with AR in lung transplant (LT) recipients. The role of Th-1 dominance expressed as IgG2/IgG1 ratio in BAL in AR was also examined. The mRNA expression for IL-2, gamma-IFN and IL-10 was examined in 64 BAL specimens from 23 LT recipients using reverse transcriptase-polymerase chain reaction (RT-PCR). IgG1 and IgG2 levels were measured in 55 BAL specimens by enzyme-linked immunosorbent assay (ELISA). The expression on mRNA for these cytokines, and the ratio of IgG2/IgG1 was correlated with AR (early AR occurring within 3 months of transplant and late AR occurring after 3 months). Ten patients had 17 episodes of biopsy proven AR. Twelve episodes of AR (6 patients) occurred within the first 3 months of transplantation. In 5 patients, AR was diagnosed 4, 5, 6, 9 and 24 months post-transplantation. Detection of gamma-IFN mRNA correlated significantly with early AR (p < 0.001), whereas it lacked correlation with late AR. Expression of IL-2 and IL-10 mRNA did not correlate with AR. IL-10 was present in most samples irrespective of the presence or absence of AR. The ratio of IgG2/IgG1 was similar in patients with or without AR. Our findings suggest that the detection of gamma-IFN mRNA in BAL by RT-PCR is useful for immune monitoring of early AR in LT recipients. Absence of elevated IgG2/IgG1 ratio, and presence of IL-10 in BAL during AR suggests that Th-1 cytokines may not be the sole mediator of rejection in LT recipients.
Moudgil
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A
Department of Pediatrics, Steven Spielberg Pediatric Research Center, Los Angeles, CA 90048, USA. moudgil@cshs.org
Bagga
A
A
Toyoda
M
M
Nicolaidou
E
E
Jordan
S C
SC
Ross
D
D
D000208:Acute Disease; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis* / Q000235:genetics; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous; D015854:Up-Regulation
D016207:Cytokines; D007074:Immunoglobulin G; D007376:Interleukin-2; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma