CYTOKINE GENE TRANSCRIPTS FOR TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-2, AND INTERFERON-GAMMA IN HUMAN PULMONARY ALLOGRAFTS

Background: Cytokines participate in host responses to allografts, lar gely through recruiting and activating various regulatory and effector cells. We performed this study to determine the feasibility of using polymerase chain reaction methodology to define the expression of thre e important cytokines (tumor necrosis factor-alpha, interleukin-2, and interferon-gamma) in human pulmonary allografts, Methods: Twenty-six graft-derived samples (11 transbronchial biopsy and 8 macrophage and 7 lymphocyte cell pellets isolated from bronchoalveolar lavage) were ob tained from 13 lung transplant recipients and treated as follows: extr action of RNA; reverse transcription of RNA to complementary DNA; poly merase chain reaction amplification of cDNA with oligonucleotide prime rs specific for the three cytokines, gel electrophoresis of the polyme rase chain reaction products; and verification of correct cytokine mes sage by Dot blot technique (with specific P-32-labeled oligonucleotide probes), Results: Concomitant pathologic evaluation of biopsy specime ns from these 13 recipients showed five diagnostic groups: ''normal'' (no rejection/infection), n = 2, acute rejection, n = 4, nonspecific i nflammation, n = 3; infection, n = 3; and obliterative bronchiolitis. n = 1. Interleukin-2 was expressed predominantly in acute rejection an d infection (seven of ten and five of six samples positive, respective ly), whereas tumor necrosis factor-alpha was expressed mainly in nonsp ecific inflammation (four of five samples) and somewhat less in reject ion (six of ten), Interferon-gamma was expressed less frequently (in t wo of six samples with infection, but in none of ten with rejection an d none of five with nonspecific inflammation). Serial data from one pa tient (6 months apart) showed considerable increase in interleukin-2 a nd interferon-gamma expression as she progressed from normal histologi c status to obliterative bronchiolitis. Conclusions: Cytokine gene tra nscripts can be determined from minute samples derived directly from p ulmonary allografts. Although our data are insufficient to make defini tive conclusions, the suggestion of trends of cytokine expression in d ifferent posttransplantation pathologic conditions may indicate a usef ul role for this approach in the clinical evaluation of the lung trans plant recipient.