CYTOMEGALOVIRUS-INFECTION IN TRANSPLANT RECIPIENTS - THE ROLE OF TUMOR-NECROSIS-FACTOR

Human cytomegalovirus (CMV) infection is an important cause of morbidi ty and mortality in transplant recipients. CMV infection commonly resu lts from the reactivation of a latent infection. Using a set of monocl onal anti-CMV antibodies, we found CMV antigen expression in periphera l blood mononuclear cells (PBMNC), particularly in monocytes, in 312 o f 816 samples from 190 allograft recipients. The detection of CMV-IE a ntigens and CMV-IE DNA in PBMNC indicates that positive cells may repr esent truly infected cells. The relation between increased cytokine pl asma levels (particularly following treatment by pan-T cell antibodies ) and the appearance of CMV antigens in PBMNC suggests that cytokines may play an important role in the reversal of CMV latency. This hypoth esis is supported by our finding that tumor necrosis factor-alpha (TNF ) is able to stimulate the activity of the CMV-IE enhancer/promoter re gion in the human monocytic cell line, HL-60. The interleukins 1, 2, 3 , 4, 6, 8 and 10; transforming growth factor-beta; interferon-gamma; a nd granulocyte/macrophage colony-stimulating factor did not show any e nhancing effect on the CMV promoter activity. Thus, TNF-alpha seems to play a key role in regulating the balance between latency and reactiv ation of CMV infection. Inhibition of TNF-alpha release or action may be an alternative strategy for preventing CMV-associated morbidity in allograft recipients.