Interferon production in severe hemophiliacs with and without HIV antibodies.

The interferon (IFN) system, both serum IFN levels and the in vitro IFN production, was investigated in 38 clinically asymptomatic multitransfused hemophiliacs, half positive and half negative for HIV antibodies. In most patients, no circulating IFN was detected; similar levels of IFN-alpha were obtained after peripheral blood mononuclear cell (PBMC) stimulation with Sendai virus both in hemophiliacs and controls, while production of IFN-gamma following stimulation with phytohemagglutin (PHA) was diminished in a large number of patients irrespective of their HIV serology. These data indicate that the deficiency in IFN-gamma generation is not only related to HIV contamination but may be a direct consequence of the chronic antigenic stimulation through Factor VIII concentrates.

Evaluation of herpes simplex virus susceptibility to acyclovir using an enzyme-linked immunosorbent assay.

An in situ ELISA was performed directly on the adherent cell monolayer in order to determine the susceptibility of herpes simplex virus isolates to acyclovir. Various fixation procedures and antisera conjugated to different enzymes were tested. The use of glutaraldehyde for fixation and beta-galactosidase as a labelling enzyme was shown to give the best results. As with other currently used assays, 50% inhibitory doses were subject to an inoculum effect. The data obtained indicate that this assay is suitable for routine determination of herpes simplex virus susceptibility to antiviral drugs.

Interferon production in severe hemophiliacs with and without HIV antibodies.

The interferon (IFN) system, both serum IFN levels and the in vitro IFN production, was investigated in 38 clinically asymptomatic multitransfused hemophiliacs, half positive and half negative for HIV antibodies. In most patients, no circulating IFN was detected; similar levels of IFN-alpha were obtained after peripheral blood mononuclear cell (PBMC) stimulation with Sendai virus both in hemophiliacs and controls, while production of IFN-gamma following stimulation with phytohemagglutin (PHA) was diminished in a large number of patients irrespective of their HIV serology. These data indicate that the deficiency in IFN-gamma generation is not only related to HIV contamination but may be a direct consequence of the chronic antigenic stimulation through Factor VIII concentrates.

In vitro antiviral activity of a saponin from Anagallis arvensis, Primulaceae, against herpes simplex virus and poliovirus.

The antiviral activity of a triterpene saponin isolated from Anagallis arvensis, Primulaceae, was studied in vitro against several viruses including herpes simplex type 1, adenovirus type 6, vaccinia, vesicular stomatitis and poliovirus. The drug was found to inhibit the replication of herpes simplex virus type 1 and poliovirus type 2 as shown by inhibition of cytopathic effect and reduction of virus production. The action was not due to a virucidal effect but might involve inhibition of virus-host cell attachment. Single cycle experiments indicated that saponin interfered with both early and late events of herpes virus replication.

[Inhibitory effects of some crude and semi-purified extracts of indigenous French plants on the multiplication of human herpesvirus 1 and poliovirus 2 in cell culture]. / Effets inhibiteurs de quelques extraits bruts et semi purifiés de plantes indigènes françaises sur la multiplication de l'herpesvirus humain 1 et du poliovirus humain 2 en culture cellulaire.

Within a valorization program of natural regional resources, 50 ethanolic extracts of 41 indigenous plants have been subjected to chemical tests and antiviral screening. Four plants: Bryonia dioìca, Anthyllis vulneraria, Matricaria chamomilla, and M. inodora inhibit the growth of poliovirus. Furthermore, three (A. vulneraria, M. Chamomilla, and M. inodora) have an antiherpetic effect.

Decrease in natural killer cell activity in kidney allograft recipients.

The natural killer cell activity (NKCA) of a population of 66 functioning kidney allograft recipients (followed up for over 9 years) was assessed on K562 and DORA cell line targets. The 51Cr specific release test showed a rapid, sharp decrease in NKCA as early as 3 months after grafting, reaching a minimal level between 7 and 60 months (5 +/- 5 vs. 45 +/- 19% 51Cr release; P less than 0.001). Patients showing an almost total lack of NKCA were roughly the same whether assessed on K562 or DORA targets. NKCA tended to be restored in long-term transplanted patients (greater than 61 months). Control populations, aside from 32 healthy individuals, consisted of 11 haemodialysed patients as well as patients submitted to corticosteroid therapy for more than one year (8 cases of giant cell arteritis and 4 chronic asthmas). Haemodialysed patients exhibited normal NKCA (whether previously grafted or not). Corticosteroid-treated patients showed either no significant modification (K562 target) or a borderline decrease (DORA target) in NKCA. Azathioprine or corticosteroid dosage intake on the day of the test did not influence the level of graft recipient NKCA. The natural cytotoxicity of peripheral blood lymphocytes (PBL) from recipients lacking in activity (less than 5% 51Cr release) was not restored by exogenous (type alpha) interferon. and PBL of recipients with low NKCA scores produced normal levels of purified interferon after 24-h Sendai virus exposure. No inhibitory effects of sera obtained from recipients lacking NKCA nor any active suppressor cells from their PBL could be evidenced, thus suggesting an actual loss of natural killer progenitors (or an "insensitivity" to interferon) in those patients. Corticosteroids, as opposed to azathioprine, were able to decrease the in vitro NKCA of healthy donor PBL at pharmacological concentrations.

[Effect of interferon on cell populations enriched in NK activity]. / Effet de l'interféron sur des populations cellulaires enrichies en activité NK.

We have studied the NK activity after either interferon action or not, in total lymphocyte populations, as well as in cellular populations enriched with NK activity. (LGL = 76 +/- 13%). The incubation with interferon lasts 16 hours at 37 degrees C. The result obtained is an increase of the NK activity of the total lymphocyte population, while the cellular population, formerly enriched with NK activity, is not affected. These results are in favour of a necessary cellular cooperation on the interferon action on NK cells.

The role of human spleen interferon on natural killer activity of peripheral blood lymphocytes enriched in large granular lymphocytes.

The elimination of monocytes as well as B- and T-lymphocytes by forming rosettes with high affinity for sheep red blood cells yielded an enriched population of both natural killer (NK) activity (cytotoxicity: 65.4 +/- 9.9% with an E/T ratio of 12:1, P less than 0.005) and large granular lymphocytes (LGL: 76 +/- 13%) compared to the untreated lymphocyte population where NK activity is 35.7 +/- 17.3% (E/T 12:1) and the percentage of LGL of 26 +/- 6%. We studied the action of type I interferon (IFN) obtained from human spleens, on NK activity of 9 peripheral blood lymphocyte populations and 9 enriched in LGL. NK activity of the total lymphocyte population is significantly increased (P less than or equal to 0.05) in 6 out of 9 cases after treatment by interferon. Cell populations enriched in LGL showed increased NK activity in only one case after treatment by interferon, but no increased activity was found in the other cases. These results are compatible with the notion of cellular cooperation in increased NK activity by interferon.

[Human spleen: a new and potent source of human interferon for experimental and therapeutic use]. / La rate humaine: une nouvelle et puissante source d'interféron humain pour usage thérapeutique et expérimental.

Cells of a single human spleen, cultivated in vitro and induced by Sendai virus, produce constantly more than 10(8) units of interferon per spleen. This interferon can be used for therapeutic assays and new basic investigations.

Large scale production of human interferon from human spleens.

In an attempt to increase the production of human interferon, human spleen appeared as a possible useful organ for large scale production of the substance. White cells provided by spleens were incubated in the presence of Sendaï Virus. Results showed that one spleen was capable to produce more than 10(8) units of interferon per spleen. The use of human spleen cells for interferon production seems interesting not only in the aim of casual therapeutic assays, but also for new basic researches on human alpha or gamma interferon, since large amounts of interferon can be obtained from a single person.

[Relations of HLA A2, A3, B12 antigens, and A2-B12 supposed haplotype association, with latent herpes virus infection in patients with chronic renal disease (author's transl)]. / Relations entre les antigènes HLA A2, A3 et B12, ainsi que l'association haplotypique présumée A2-B12 et une infection herpétique latente chez des malades atteints d'insuffisance rénale chronique.

Comparison of 105 patients suffering of chronical renal failure with 108 normal persons showed that, in the former group, a relation could be established between HLA A2, A3, and B12 histocompatibility antigens as well as haplotype association A2-B12, and chronic infection by herpes virus. The high number of herpes virus observed in patient group bearing the BW 35 antigen was discussed.

[Production of interferon after infection by various doses of "Plasmodium berghei" in mice (author's transl)]. / Interféron produit chez la souris après infection par des doses variées de Plasmodium berghei.

Groups of mice were inoculated with either low or high intraperitoneal doses of Plasmodium berghei infected erythrocytes (PIE). The course of infection was observed daily by counting new PIE which appeared in the red blood cells (RBC) of infected mice. At the same time, circulating interferon (IF) was tested. When low doses of infecting PIE were used (400 per mouse), circulating IF was first detected on the 5th day after inoculation. It increased to a maximal rate, when 5% of RBC were affected. It disappeared on the 8th day despite of a continuous rise of PIE. With high doses of PIE (60,000 per mouse), IF was detected on the 3rd day, when only 0.5% of RBC were parasitized. The maximal rate was observed on the 5th day when 20% of the RBC were affected. It disappeared on the 7th day, though the PIE rate would continue to rise. Treatment of mice by chloroquine (0.01 per g), at the time of first PIE appearance after Plasmodium infection, rapidly reduced the amount of PIE. In this case, no IF production was observed. Splenectomy resulted in an increased resistance of mice to the lethal effect of Plasmodium infection. IF production in such splenectomized mice was less important than in control. It was concluded that P. berghei was a good inducer of circulating IF at the beginning of the active disease, soon after infection. The fact was proven by the striking lowering effect of chloroquine and splenectomy that both reduced Plasmodium development and IF production.

The protective effect of endogenous interferon in mouse malaria, as demonstrated by the use of anti-interferon globulins.

Both death rate and percentage of parasitized erythrocytes in mice infected with Plasmodium berghei were enhanced by injections of anti-interferon globulins. As, in the same time, parasite-induced interferon was neutralized by these globulins, it can be concluded that endogenous interferon plays an important inhibiting role during parasitic diseases, such as malaria, as it has been previously demonstrated in many virus infections.