Controlled Clinical Trial of Prophylactic Human-Leukocyte Interferon in Renal Transplantation

Abstract

A double-blind, placebo-controlled trial of interferon prophylaxis against viral infections was conducted in renal-transplant recipients receiving standard immunosuprressive therapy with or without antithymocyte globulin. Interferon was administered for six weeks, beginning on the day of transplantation. Cytomegalovirus excretion began earlier and viremia was more frequent in placebo-treated than in interferon-treated patients. Cytomegalovirus viremia correlated with clinical syndromes was more frequent in recipients of antithymocyte globulin. In contrast, neither interferon nor antithymocyte globulin altered excretion of herpes simplex virus. Reversible leukopenia and thrombocytopenia occurred in seven interferon recipients. Patient and graft survival were comparable in interferon and placebo groups. There preliminary results suggest that a six-week course of prophylactic interferon delays shedding of cytomegalovirus and decreases the incidence of viremia after transplantation. In contrast, antithymocyte globulin appears to increase the severity of infection from cytomegalovirus among these patients.

High levels of circulating cytomegalovirus DNA reflect visceral organ disease in viremic immunosuppressed patients other than marrow recipients.

“…Among marrow recipients, viremia may be subclinical, although it is clearly a major risk factor for the development of interstitial pneumonitis, which is often fatal ( 10,19,20,24). In solid organ transplant patients, viremia may not be associated with symptoms or may result in a "CMV syndrome," characterized by varying combinations offever, musculoskeletal symptoms, leukopenia, atypical lymphocytosis, thrombocytopenia, and liver dysfunction (25)(26)(27)(29)(30)(31)(32)(33). However, visceral organ CMV disease may develop, most frequently in the lungs (27,(31)(32)(33)(34).…”

CD11c+ dendritic cells and plasmacytoid DCs are activated by human cytomegalovirus and retain efficient T cell-stimulatory capability upon infection

“…Disruption of IFN type 1 signaling in IFNR-␣␤ knockout mice renders them highly susceptible to MCMV infection, 31 and prophylactic administration of IFN-␣ prevents HCMV reactivation in patients who have undergone transplantation. 32,33 Yet the resistance of human PDCs to HCMV infection appeared to be independent of secreted IFN type 1 because frequencies of IEA-positive cells were lower than 4%, even in the presence of antibodies blocking IFN type 1 signals. A possible explanation could be that PDCs are continuously stimulated by autocrine low-level constitutive secretion of IFN-␣ and, hence, are already primed for HCMV resistance.…”

Beta interferon plus gamma interferon efficiently reduces acyclovir-resistant herpes simplex virus infection in mice in a T-cell-independent manner

“…A short-term prophylaxis therapy using leukocyte IFN or ACV reduces infection in these patients (Cheeseman et al, 1979;Horsburgh et al, 1998). In the present study, topical treatment with a low dose of IFN-b plus IFN-c efficiently reduced the replication of ACV-resistant HSV-1 in mouse tissues, particularly when the treatment was given before or early after infection.…”

“…Prophylactic treatment with leukocyte IFN has been shown to reduce HSV infection in patients who have undergone renal transplantation or a trigeminal root operation (Cheeseman et al, 1979;Pazin et al, 1979). Recent in vitro studies showed that IFN-b and IFN-c act synergistically to reduce the replication of several viruses, including HSV-1 (Larkin et al, 2003;Peng et al, 2008;Sainz & Halford, 2002;Sainz et al, 2004Sainz et al, , 2005.…”