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...
Of 37 patients with herpes zoster 28 were treated with human exogenous interferon and 9 received only culture medium. The interferon was produced in leukocyte cultures and was given intramuscularly in one daily dose of 1 million units for 5-8 days. In the interferon-treated patients interferon was detectable in serum (peak level 1-5 hours after interferon injections) and in vesicle fluid, and in some patients also in urine samples. Anti-interferon antibodies were not found. Of the 28 interferon-treated patients 8 had a slight temperature increase and 4 showed a transient local reaction. In the interferon treated group of patients the duration of pain was shortened and the development of crust formation was enhanced compared with the control group.
Despite their limited ability to synthesize immunoglobulins (only IgA and not IgM or IgG) lymphocytes of human colostrum and human breast milk can be stimulated by Newcastle disease virus to produce interferon in the same amount as do blood lymphocytes. The maximum interferon production by milk lymphocytes was found on the 4th and the 5th day postpartum.
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