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Treatment of Rhesus monkeys with human leukocyte interferon prevents the development of skin lesions after intradermal infection with vaccinia virus. The treatment does not prevent the development of immunity to vaccinia. Inactivated vaccinia virus, which is non-immunogenic in untreated monkeys, induced immunity under interferon treatment, indicating that interferon had an immunestimulating effect.

Cytomegalovirus (CMV) seropositivity is associated with increased risk for atherosclerotic disease in patients with end-stage renal disease. This association is due to a unique peripheral blood CD4(+) T cell population which lack CD28 (CD4(+)CD28(-) T cells). Here we found that this patient population has a significant age-dependent increase of CD4(+)CD28(-) T cells that comprise over half of the circulating CD4 T cells in some. Patients over 50 years of age have a 50-fold higher percentage of CD4(+)CD28(-) T cells compared to seronegative patients and a 5-fold higher percentage when compared to seropositive healthy controls. Stimulation by CMV-antigen or by polyclonal stimulation using PMA and ionomycin showed that CD4(+)CD28(-) cells in patients with end stage renal disease degranulated and secreted interferon gamma thus indicating that they are cytolytic. The average anti-CMV IgG titer displayed a remarkable age-dependent increase only in patients with end stage renal disease. These findings are highly suggestive of repetitive antigenic stimulation of the immune system in patients with end stage disease by subclinical CMV reactivation which might contribute to increased atherosclerotic risk.

Terminal kidney patients are faced with lower quality of life, restricted diets and higher morbidity and mortality rates while waiting for deceased donor kidney transplantation. Fortunately, living kidney donation has proven to be a better treatment alternative (e.g. in terms of waiting time and graft survival rates). We observed an inequality in the number of living kidney transplantations performed between the non-European and the European patients in our center. Such inequality has been also observed elsewhere in this field and it has been suggested that this inequality relates to, among other things, attitude differences towards donation based on religious beliefs. In this qualitative research we investigated whether religion might indeed (partly) be the explanation of the inequalities in living donor kidney transplants (LDKT) among non-European patients. Fifty patients participated in focus group discussions and in-depth interviews. The interviews were conducted following the focus group method and analyzed in line with Grounded Theory. The qualitative data analyses were performed in Atlas.ti. We found that religion is not perceived as an obstacle to living donation and that religion actually promotes helping and saving the life of a person. Issues such as integrity of the body were not seen as barriers to LDKT. We observed also that there are still uncertainties and a lack of awareness about the position of religion regarding living organ donation within communities, confusion due to varying interpretations of Holy Scriptures and misconceptions regarding the process of donation. Faith leaders play an important educational role and their opinion is influential. This study has identified modifiable factors which may contribute to the ethnic disparity in our living donation program. We argue that we need to strive for more clarity and awareness regarding the stance of religion on the issue of living donation in the local community. Faith leaders could be key figures in increasing awareness and alleviating uncertainty regarding living donation and transplantation.

Twenty-three cadaveric renal allograft recipients with stable but compromised kidney function were electively converted from cyclosporine to azathioprine one year after transplantation. Within a few weeks glomerular filtration rate (GFR) rose by 40% and serum creatinine fell from 171 +/- 12 (mean +/- SEM) to 129 +/- 7 mumol/L. The increase in GFR was due to an increase in effective renal plasma flow of 21%. This suggests that one year of continuous cyclosporine (CsA) therapy does not result in irreversible structural renal damage. Although antihypertensive treatment was not changed, blood pressure fell from 142 +/- 4/90 +/- 3 to 123 +/- 3/77 +/- 2 mmHg. In addition a significant drop in serum cholesterol and triglycerides and an improvement in glucose tolerance were found. The beneficial effects on renal function, blood pressure, and metabolic indices were, however, outweighed by a high incidence of postconversion rejection in recipients of a second allograft. For these patients conversion from CsA to azathioprine seems therefore contraindicated. Recipients of a first kidney allograft can be converted safely, as long-term CsA administration in these patients induced a solid engraftment. The sequelae of the mode of treatment--impaired renal function, hypertension, and metabolic disturbances--are reversible even after late conversion.

The incidence of osteonecrosis was 24% in 248 patients who had received 262 kidney transplants 1971-1982. However, based only on patients at risk, i.e. alive with functioning transplants, the incidence at 1, 3 and 6 years was found to be 13, 27 and 36%; after six years no new cases were found. The relative increase in body-weight at 180 days was predictive as regards risk for osteonecrosis, while the cumulative dose of steroids was not. This suggests that individual sensitivity to steroids rather than the absolute cumulative dose is involved in the development of osteonecrosis.

Recently a series of 5-halo-6-phenyl pyrimidinones has been found to induce interferon production in several animal species (Stringfellow et al., 1980) and in man (Earhart et al., 1985). These compounds modulate a variety of immune responses. Most prominently they enhance the activity of natural killer (NK) cells (Taggert et al., 1980) and macrophages (Li et al., 1985). In the experiments reported here we evaluated the effects of two pyrimidinones that differ greatly in their ability to induce interferon (IFN) production. ABPP (2amino-5-bromo-6-phenyl-4-pyrimidinone) induces high serum levels of IFN whereas AIPP (2-amino-5iodo-6-phenyl-4-pyrimidinone) does not. Yet, both agents are equally active in enhancing NK cell activity (Lotzova et al., 1983). In a previous communition (Marquet et al., 1983) we have shown that subcutaneous growth of liposarcoma LS175 in BN rats is inhibited by IFN. This nonimmunogenic liposarcoma is of spontaneous origin and has been found to be NK resistant. In order to investigate whether the induction of IFN plays a part in the antitumour effects of ABPP and AIPP we compared the two agents in the subcutaneous and in the artificial lung metastasis model, using tumour LS175. Ten to 12-week old male BN rats were used in all experiments. The NK cell activity in peripheral blood lymphocytes (PBL) after the intraperitoneal administration of 250mg kg-1 of ABPP or AIPP was assessed by a standard 3 h IICr release assay as described by Ortaldo et al. (1977). Control animals received an equal volume of PBS i.p. The results are shown in Figure 1. A rapidly established and longlasting +4-fold increase in NK cell cytotoxicity is seen after the administration of either agent. The influence on macrophage activity was assessed by measuring the ingestion of latex

Plasma atrial natriuretic factor (ANF) concentrations were measured, and relationships to intracardiac pressures and atrial dimensions were assessed in a series of 17 heart transplant recipients undergoing cardiac catheterization during their annual evaluation. Despite excellent cardiac function (normal filling pressures, adequate cardiac output, ejection fraction above 60%), plasma levels of ANF were elevated. Step-up levels across the heart were consistent with increased cardiac secretion, whereas both the metabolic clearance rate and plasma half-life were normal. Correlations between plasma concentrations of ANF at different cardiac sites and atrial filling pressures were low. However, right and left atrial dimensions in our patients were greatly enlarged. These findings suggest that increased atrial size (by virtue of the atrial anastomoses) and augmented wall stress (law of Laplace) rather than pressure per se are responsible for the increased ANF production after heart transplantation.

In an attempt to determine the safety, tolerance, and prophylactic antiviral activity of high doses of recombinant DNA leucocyte interferon A a double-blind parallel-group study was started in 16 renal transplant recipients. All 16 patients had early rejection episodes. In all 8 interferon-treated patients and 1 placebo-treated patient this rejection, which was of the acute vascular humoral type, was steroid resistant. 3 interferon-treated patients also had transient nephrotic syndrome.

We have studied the concanavalin A (ConA)-induced interferon gamma (IFN-gamma) production of peripheral blood mononuclear cells (PBMC) of renal allograft recipients. Both under immunosuppressive treatment with azathioprine and with cyclosporin A (CsA) the PBMC of these patients proved deficient for IFN-gamma production when compared to those of healthy controls. After conversion from conventional azathioprine to CsA medication the ConA-induced IFN-gamma production increased.

Toxoplasma gondii infections in heart transplant recipients were monitored by indirect enzyme-linked immunosorbent assay for immunoglobulin G (ELISA-IgG), indirect ELISA-IgM in serum IgM fractions, antibody capture ELISA-IgM, IgM-immunosorbent agglutination assay (ISAGA), and IgM immunoblotting. Basic immunosuppression consisted of cyclosporine and low-dose steroids. Before transplantation, 26 of 43 recipients showed serological evidence of infection. In serum samples from 15 (35%) recipients, specific antibodies were not detected. Approximately 50% of the heart donors, were toxoplasma seropositive. Eight of the fifteen seronegative recipients received hearts from toxoplasma-seropositive donors. In four of the eight recipients, seroconversion could be demonstrated with all tests used. In three of these four patients, clinical disease developed. One patient with strong serological evidence of toxoplasmosis died, but toxoplasma parasites and antigens were not detected at autopsy. In two patients, toxoplasma cysts were found in cardiac biopsies. Seroconversion was not prevented by the use of spiramycin prophylaxis in two recipients. Reactivations of latent infections or reinfections were detected by indirect ELISA in six (23%) seropositive recipients, but symptoms and signs of active T. gondii infection were not seen. Seroconversion and reactivation of infection were readily found by a combined use of indirect ELISA-IgG and ELISA-IgM and antibody capture ELISA-IgM. Discrepancies in results could be examined by immunoblotting. IgM-ISAGA retained stable positive values longer than IgM-ELISAs did. Cyclosporine treatment did not hamper detection of seroconversion but could cause antibody levels to remain relatively low in primary infections. Seronegative recipients should receive antitoxoplasma treatment on seroconversion.

Auxiliary heterotopic liver transplantation is theoretically attractive because it leaves the recipient's liver in place. The surgical trauma of hepatectomy is avoided, and failure of the graft does not necessarily lead to the death of the patient or a second, emergency transplantation. Another advantage is that matching the body sizes of the donor and the recipient is not mandatory, which increases the number of possible donors. However, previous clinical results of auxiliary liver transplantation have been poor. We performed auxiliary partial liver transplantation in six consecutive patients with end-stage chronic liver disease who were not accepted for orthotopic liver transplantation because they had massive ascites, deficient clotting function, cachexia, or poor pulmonary reserve. The donor liver was transplanted to the right subhepatic region after removal of segments II and III, and it was provided with portal and arterial blood. There were no major changes in hemodynamic measurements during surgery. The mean hospital stay after transplantation was 22.7 days (range, 14 to 29). After a mean follow-up period of 14 months (range, 5 to 23), all patients were alive, with good graft function as demonstrated by scintigraphy, Doppler ultrasonography, and synthesis of clotting factors. From these observations we conclude that auxiliary partial liver transplantation is an attractive alternative to orthotopic liver transplantation in high-risk patients. Its role in other patients who need liver transplants remains to be defined.

An assay is described for handling clinical specimens for the detection of cytomegalovirus. It consists of low-speed centrifugation of the specimen on human embryonic lung cells, using a technique adapted from chlamydial culture, followed by detection using a monoclonal antibody against the cytomegalovirus early antigen in an immunofluorescence technique. This assay was compared with the conventional cell culture system. 161 specimens obtained from 52 patients were studied; from 14 patients CMV was isolated in at least one specimen (in total 28 specimens). The centrifugation technique led to positive results generally within 24 to 48 h, whereas the cell culture took an average of 16.5 days to develop the typical cytopathic changes. No cross-reactions between the cytomegalovirus monoclonal antibody and other viruses present (herpes simplex virus and adenovirus) were observed. The centrifugation technique is a reproducible and rapid method in the diagnosis of cytomegalovirus infection.

The prophylactic antiviral activity of systemically administered human interferon preparations was tested in 36 rhesus monkeys against vaccinia virus injected into the skin. All nine control monkeys developed typical vaccinia skin lesions. Eight of nine monkeys treated with daily intramuscular injections of leucocyte interferon (5 x 10(5) units/kg) from day -1 to day +7 after vaccination were completely protected. No lesions developed after discontinuation of therapy. Administration of the same amounts of leucocytic interferon intravenously (i.v.) was equally effective. Daily intramuscular (i.m.) injections of lower doses of leucocyte interferon (1.25 c 10(5) units/kg; 0.5 x 10(5) units/kg) decreased the severity of the skin lesions. Lesion scores correlated inversely with the dose of interferon. Four of six animals receiving daily i.m. injections of fibroblast interferon (5 x 10(5) units/kg) and one of three animals treated i.v. with the same dose were protected against vaccinia virus, and the lesions in the other monkeys were smaller. Intramuscular injections of 5 x 10(5) units/kg of fibroblast interferon or 1.25 x 10(5) units/kg of leucocyte interferon resulted in comparable serum levels and had comparable efficacy in reducing lesion scores.

In a double-blind trial renal allograft recipients were treated with fibroblast interferon preparations for 3 months in an attempt to prevent viral infections. Interferon therapy did not reduce the overall incidence of viral infections. No adverse effects were noted on liver function, platelet counts. or leucocyte counts, or acute rejection episodes.

A total of 20 patients with advanced colorectal cancer received recombinant leukocyte interferon-alpha A (rIFN alpha A) either chronically (group I: twice a week up to 20 X 10(6) IU/m2 i.m.) or cyclically (group II: 1-4 periods of 8 consecutive days up to 20 X 10(6) IU/m2 i.m. daily at 20-days intervals) over a period of 12 weeks. There was 1 partial response, 1 mixed response and 1 patient with stable disease, whilst 17 patients had progressive disease. Median survival was 15.5 months. Survival was significantly shorter when the extent of hepatic disease was greater than 25% (P = 0.05), extrahepatic disease was extensive (P less than 0.005), alkaline phosphatase level was greater than 2 X normal (P less than 0.02), or performance status was less than 100% (P less than 0.001). Toxicity consisting mainly of fever, fatigue, anorexia and weight loss was serious in group I and minimal in group II. Administration of rIFN alpha A led to a "short lived" augmentation of natural killer (NK) cell activity. In the cyclically treated group this was a recurrent phenomenon whereas a marked lasting depression of NK cell activity was seen in chronically treated patients. Interferon-gamma production capacity was significantly stimulated during rIFN alpha A therapy. The differences in toxicity and immunostimulatory effects between the two schedules may be of importance in the design of further studies.

In a double-blind study human leucocyte interferon was given for six weeks to 8 of 16 patients with chronic HBsAg-positive hepatitis. In the first week 12×10 6 reference units were administered daily, and thereafter the dose was halved every week. During the first two weeks leucopenia was observed in 6 of the 8 interferon-treated patients. Apart from a drop in DNA-polymerase activity in the first week, no effect was found on indices of hepatitis-B-virus infection.

The influence of the cytomegalovirus (CMV) serostatus of blood and kidney donors on patient and graft survival was studied prospectively in 73 cadaveric renal graft recipients. Six out of 12 (50%) CMV seronegative recipients receiving a kidney from a CMV seropositive donor developed CMV disease, in contrast to none of 7 CMV seronegative donor/recipient combinations. Transmission of CMV with blood products to seronegative recipients was not observed in this study. A poor graft survival of 41% 3 years after transplantation was found in CMV seronegative recipients with CMV seropositive allograft donors, compared with an actuarial 3 year graft survival of 72% in the 7 CMV seronegative donor/recipient combinations. Six patients with graft failure had a CMV infection. This study, in accordance with other studies, suggests that selection of CMV seronegative renal allograft donors for CMV seronegative recipients will improve graft survival.

One hundred and one patients on haemodialysis, 21 patients on peritoneal dialysis and 30 healthy controls received a trivalent split vaccine containing 15 micrograms haemagglutinin of a recent influenza A-H3N2, influenza A-H1N1 and influenza B strain, respectively. Antibody production after four weeks was determined by the haemagglutination-inhibition test and expressed as response rate, protection rate and overall mean fold increase. The patients on haemodialysis revealed a diminished seroresponse, as compared to patients on peritoneal dialysis and controls. For influenza A-H3N2, this was less distinct than for the other two antigens. In patients on haemodialysis the protection rate was 66% against the A-H3N2 vaccine component (versus 85% in controls, not significant), but only 25% against A-H1N1 and 27% against B (versus 84 and 77% in controls, p less than 0.001). Duration of haemodialysis up to eight years did not affect seroresponse. Patients on haemodialysis who were primed for influenza A-H1N1 in the period 1947-1957, reacted markedly better to the A-H1N1 vaccine component than subjects of other priming periods. A booster injection of the same vaccine dosage four weeks after the first immunization, performed in 98 patients on haemodialysis, was of little value: it had virtually no effect with regard to influenza A-H1N1 and influenza B, and showed, though significantly better, still poor results for A-H3N2. The differences in seroresponse between the A-H3N2 and A-H1N1 vaccine component suggest a major defect of primary, and a minor defect of secondary humoral response in patients on haemodialysis. The consequences for vaccine policy in these patients are discussed.

After influenza vaccination no statistically significant difference in antibody response was observed between patients on continuous ambulatory peritoneal dialysis (CAPD) and healthy volunteers while a large group of hemodialysis (HD) patients was found to have a significantly lower response rate. This difference remained statistically significant when CAPD patients were compared to a matched HD group. As the antibody formation after influenza vaccination is a T cell-dependent phenomenon, the normal immune response to vaccination suggests an intact humoral and cellular immunity in CAPD patients.

The effect of cytomegalovirus (CMV) disease on mononuclear subpopulations of 49 renal transplant recipients treated with cyclosporine and prednisone are reported. Clinical overt CMV infection developed in 8/21 patients treated for rejection with rabbit antithymocyte globulin. They all showed true inversions of the T helper/T suppressor-cytotoxic (Th/Ts-c) ratio. A reduction of T helper cells and increase in T suppressor-cytotoxic cells preceded clinical symptoms of CMV disease by one week. None of the 26 patients without RATG anti-rejection treatment developed CMV disease and in only three of them an inversion of Th/Ts-c ratio was found.

Focal small mononuclear cell infiltrates were found in renal allograft biopsies of 13/14 transplant recipients with a stable function after long-term cyclosporin A (CsA) therapy. Phenotypical analysis of the infiltrating cells using monoclonal antibodies showed a slight preponderance of T cells (56% +/- 8%), with only small percentages of B cells (5% +/- 2%), NK cells (2% +/- 1%), and monocytes (2% +/- 1%). Within the T-cell population the median calculated CD4/CD8 ratio was 1:3. Thirty-five percent of the infiltrating mononuclear cells remained unidentified with the monoclonal antibody panel used (silent cells). Three months after immunosuppressive therapy had been changed from CsA to azathioprine (AZA), the size of the infiltrates was significantly increased and there was a marked invasion of mononuclear cells between tubular epithelium despite a significant improvement in creatinine clearance (P less than 0.01). the phenotypical composition of these infiltrates was dominated by T cells (84% +/- 3%), with a median CD4/CD8 ratio of 2:7 due to an increase in CD4+ cells and a decrease in CD8+ after conversion (P less than 0.05). The percentages of B cells, NK cells, and monocytes showed no significant changes after conversion. During AZA therapy nearly all infiltrating mononuclear cells were stained with the monoclonals used, leaving no silent cells postconversion.

Item does not contain fulltext Conversion of potential organ donors to actual donors is negatively influenced by family refusals. Refusal rates differ strongly among countries. Is it possible to compare refusal rates in order to be able to learn from countries with the best practices? We searched in the literature for reviews of donor potential and refusal rates for organ donation in intensive care units. We found 14 articles pertinent to this study. There is an enormous diversity among the performed studies. The definitions of potential organ donors and family refusal differed substantially. We tried to re-calculate the refusal rates. This method failed because of the influence caused by the registered will on donation in the Donor Register. We therefore calculated the total refusal rate. This strategy was also less satisfactory considering possible influence of the legal consent system on the approach of family. Because of lack of uniform definitions, we can conclude that the refusal rates for organ donation can not be used for a sound comparison among countries. To be able to learn from well-performing countries, it is necessary to establish uniform definitions regarding organ donation and registration of all intensive care deaths.

As our knowledge of the cytokine network in experimental transplant models grows, we need to understand how and to what extent cytokines mediate the various donor-directed immune events in clinical situations. This overview of clinical cytokine measurements shows that specific intragraft cytokine messenger RNA (mRNA) expression profiles can be associated with acute rejection, that they may reflect the efficacy of immunosuppression, and that they can identify patients at risk for the development of early chronic rejection. The literature also shows that acute rejection and immunological quiescence in humans are not restricted to the cytokine patterns defined in the type 1/type 2 paradigm. This apparent lack of association may be caused by the immunosuppression used in the clinic but may also be the result of the infinite diversity of donor and recipient factors, in which polymorphisms in cytokines and cytokine receptor genes may play a central role.

Background: The aim of this study was to investigate whether pretransplant tacrolimus (Tac) dose requirements of patients scheduled to undergo living donor kidney transplantation correlate with posttransplantation dose requirements. Methods: The predictive value of Tac dose requirements (defined as the ratio of the Tac predose concentration, C-0, divided by the total daily Tac dose, D) pretransplantation on this same parameter posttransplantation was assessed retrospectively in a cohort of 57 AB0-incompatible kidney transplant recipients. These patients started immunosuppressive therapy 14 days before transplant surgery. All patients were using a stable dose of glucocorticoids and were at steady-state Tac exposure before transplantation. Results: Tac dose requirements immediately before transplantation (C-0/D-before) explained 63% of the Tac dose requirements on day 3 after transplantation: r(2) = 0.633 [F (1, 44) = 75.97, P < 0.01]. No other clinical and demographic variables predicted Tac dose requirements early after transplantation. Conclusions: Steady-state Tac dose requirement before transplantation largely predicted posttransplantation Tac dose requirements in AB0-incompatible kidney transplant recipients. The importance of this finding is that the posttransplantation Tac dose can be individualized based on a patient's pretransplantation Tac concentration/dose ratio. Pretransplant Tac phenotyping therefore has the potential to improve transplantation outcomes.

Alloreactive T lymphocytes are the initiators and effectors of acute rejection of organ transplants, and T cells with high-affinity receptors for antigen might be especially implicated in this process. It has been shown that the cytotoxic capacity of CTL with low affinity for alloantigens can be inhibited with CD8 mAb, while high-affinity CTL are not affected. To investigate whether the presence of such high-affinity cells in human heart transplants may be predictive for acute rejection, we analyzed their frequency in cultures derived from endomyocardial biopsies in 19 patients, 9 of whom had never experienced acute rejection and 10 who had had one or more rejection episodes. IN the rejectors, already before histological signs of rejection (myocyte damage) had developed, significantly higher donor-reactive CTL frequencies were found compared with the nonrejectors (medians of 10,586 vs 1,169 reactive cells per 10(6) tested cells, P = 0.002). After CD8 inhibition, the difference between rejectors and nonrejectors was even more pronounced (P < 0.001). In patients with rejection, the number of CD8-resistant, high-affinity CTL was higher than 1000 per million cells in all cases, while in patients who had never experienced rejection this number was less than 1000. As these CTL characteristics are already present before the first histological signs of rejection have developed, this might be used as a prognostic factors.

Kidney exchange donation programs offer a good solution to help patients with a willing, but incompatible living kidney donor. Literature shows that blood type O patients are less likely to be selected for transplantation within a living exchange donation program. 'Altruistically unbalanced donation' could help these blood type O patients: one donor-recipient pair is incompatible (e.g. A-donor > O-recipient) and the other pair is compatible, but not identical (e.g. O-donor > A-recipient). Exchanging these kidneys would result in two compatible living donor kidney transplants. We studied whether compatible pairs would be willing to participate in such procedure. We included 96 living kidney donors and recipients in our study. These donors and recipients could be divided into two groups: (i) donors and their direct recipients (n = 48), and (ii) paired exchange donors and their intended recipients (n = 48). All were asked whether they would be willing to participate in altruistically unbalanced exchange donation, as long as direct donation was also an option. We found no group differences. We found that one third of the donors and recipients are willing to participate in altruistically unbalanced kidney exchanges. Therefore this form of donation may be a feasible addition to already existing living kidney exchange programs.

This overview describes the full spectrum of current pre-clinical and clinical kidney-, liver-, heart- and lung transplantation research performed in Erasmus MC - University Medical Centre in Rotterdam, The Netherlands. An update is provided on the development of a large living donor kidney transplantation program and on optimization of kidney allocation, including the implementation of a domino kidney-donation program. Our current research efforts to optimize immunosuppressive regimens and find novel targets for immunosuppressive therapy, our recent studies on prevention of ischemia-reperfusion-induced graft injury, our newest findings on stimulation of tissue regeneration, our novel approaches to prevent rejection and viral infection, and our latest insights in the regulation of allograft rejection, are summarized.

Wegener's granulomatosis affects renal function in the majority of cases by a focal necrotizing glomerulonephritis. In this case report we describe a patient in whom ureteral obstruction due to a retroperitoneal localization preceded this renal manifestation.

INTERFERON has antiviral effects both in vivo and in vitro. Viral replication is inhibited in interferon-treated cells in vitro because the reproductive cycle of the virus is inhibited at the transcriptional or translational level, depending on the virus–cell system studied1. This direct inhibition of viral replication has been assumed to also be the mechanism by which interferon exerts its antiviral effect in vivo. We report here results that indicate protection by interferon against viral infection in vivo without inhibition of the viral replication of the same virus in vitro.

Necessite de doses augmentees parce que les reponses en anticorps sont diminuees chez les malades sous hemodialyses