Effect of Human Exogenous Leukocyte Interferon in Cytomegalovirus Infections

Abstract

Human leukocyte interferon was injected into nine patients with cytomegalovirus infections; four of these patients were congenitally infected, and five had acquired infections. In three patients viruria was completely inhibited. In five patients viral excretion in the urine was only transiently inhibited. Viremia was not significantly suppressed. The lymphocyte response to phytohemagglutinin was suppressed in two patients.Cytomegalovirus (CMV) has been associated with long-term, chronic infections in humans and causes the most common type of congenital infection. CMV has the ability to cross the placenta and to produce chronic infection in the fetus; such infection leads to serious pathologic changes or death. About 1.5% of all newborns excreting CMV in the urine after birth in one study [1] and approximately 3.3 % of viruric newborns in other studies [2,3] have had the classical signs of congenital CMV infection. Disseminated infection with CMV occurs in adults who have malignancies or who are taking corticosteroids [4], in children with leukemia [5,6] or lymphosarcoma [7], and in patients who have had renal or bone-marrow transplantation [8,9].There is no established treatment for congenital or disseminated infection with cytomegalovirus. Only a few studies employing adequate virological monitoring of antiviral chemotherapy have been reported, and these studies revealed variable results in a small number of patients. FIuorodeoxyuridine, iododeoxyuridine, or cytosine arabinoside did not significantly alter the clinical course of illness or viral excretion [10][11][12].Evidence exists that interferon may be one de- terminant of host resistance to viral infections [13][14][15]. In a non randomized study we have observed a possible antiviral effect of exogenous human leukocyte interferon in the treatment of local and generalized infections with herpes simplex virus and varicella-zoster virus [15,16]. Falcoff has reported a beneficial effect of exogenous amniotic interferon in the treatment of congenital CMV infection [17]. Our study was initiated to examine the effect of human leukocyte interferon on the rate of excretion of CMV in the urine and in fractions of the buffy coat of patients who are chronic carriers of CMV. Materials and MethodsHuman leukocyte interferon was prepared in our laboratory. Details regarding production, purification, standardization, and sterilization of this preparation have been described previously [15]. Interferon levels in administered preparations were assayed by microtitration techniques; vesicular stomatitis virus was inhibited in human foreskin fibroblast monolayers [18].Isolations of virus from urine, leukocytes, and lymphocytes were based on growth and cytopathological characteristics. Clean urine was collected daily for a period of at least 20 days and processed immediately. Each of five tubes of confluent cultures of WI-38 human fibroblasts in Eagle's minimal essential medium (MEM) containing 2% inactivated fetal calf serum was inoculated with 0.4 ml of MiIIipore-filtered urin...

Human Cytomegalovirus Utilizes a Nontraditional Signal Transducer and Activator of Transcription 1 Activation Cascade via Signaling through Epidermal Growth Factor Receptor and Integrins To Efficiently Promote the Motility, Differentiation, and Polarization of Infected Monocytes

“…Studies of the specific effects of IFN-like responses on the HCMV viral life cycle have produced conflicting results. For example, it has been reported that IFN treatment does little to inhibit the viral life cycle (53,54), while other reports indicate that IFNs are effective at the inhibition of HCMV replication (55,56). To add greater complexity to the potentially diverse role for IFN responses in HCMV infection, IFN-␥, when combined with tumor necrosis factor alpha (TNF-␣), was shown to produce an HCMV replicationpermissive macrophage that was resistant to future IFN-␥-induced cytokines (57).…”

Susceptibility of Clinical Isolates of Cytomegalovirus to Human Interferon

“…Administration of massive interferon doses may also affect CMV excretion in the urine. Viruria was completely inhibited in three ofnine patients with congenital or acquired infection treated by Emodi et al (6), and in five patients, viruria was transiently suppressed. Viremia was not affected.…”

Interferon Induction in Human Leukocytes after in vitro Exposure to Cytomegalovirus or Epstein-Barr Virus

“…IFN of all types reduces CMV early and late antigen induction in fibro blasts in vitro [our unpublished data]. When IFN has been administered in vivo to pa tients with acute CMV infections, the results have been variable [38][39][40][41], There are indica tions that it may be useful for prophylaxis, delaying CMV infection in renal or bone marrow transplant recipients [42]. Similarly, IFN diminished EBV excretion in renal transplant recipients when given prophylactically [43].…”