Expression of Γ‐IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients

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Abstract
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 Γ‐interferon (Γ‐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, Γ‐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 of 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 Γ‐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 Γ‐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.