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

Clin Transplant. 1999 Apr;13(2):201-7. doi: 10.1034/j.1399-0012.1999.130208.x.

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 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.

MeSH terms

  • Acute Disease
  • Biopsy
  • Bronchoalveolar Lavage Fluid / immunology*
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation
  • Graft Rejection / immunology*
  • Graft Rejection / pathology
  • Humans
  • Immunoglobulin G / analysis
  • Interferon-gamma / analysis*
  • Interferon-gamma / genetics
  • Interleukin-10 / analysis
  • Interleukin-10 / genetics
  • Interleukin-2 / analysis
  • Interleukin-2 / genetics
  • Lung Transplantation / immunology*
  • Lung Transplantation / pathology
  • Male
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Time Factors
  • Transplantation, Homologous
  • Up-Regulation

Substances

  • Cytokines
  • Immunoglobulin G
  • Interleukin-2
  • RNA, Messenger
  • Interleukin-10
  • Interferon-gamma