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Expression of gamma-IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients.
Moudgil A; Bagga A; Toyoda M; Nicolaidou E; Jordan SC; Ross D;
July 30, 1999
Clin Transplant. 1999 Apr;13(2):201-7. Unique Identifier : AIDSLINE

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.

JOURNAL ARTICLE Acute Disease Biopsy Bronchoalveolar Lavage Fluid/*IMMUNOLOGY Cytokines/IMMUNOLOGY Enzyme-Linked Immunosorbent Assay Female Follow-Up Studies Gene Expression Regulation Graft Rejection/*IMMUNOLOGY/PATHOLOGY Human IgG/ANALYSIS Interferon Type II/*ANALYSIS/GENETICS Interleukin-10/ANALYSIS/GENETICS Interleukin-2/ANALYSIS/GENETICS Lung Transplantation/*IMMUNOLOGY/PATHOLOGY Male Polymerase Chain Reaction RNA, Messenger/*ANALYSIS/GENETICS Th1 Cells/IMMUNOLOGY Th2 Cells/IMMUNOLOGY Time Factors Transplantation, Homologous Up-Regulation (Physiology)