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Many drugs are know to be capable to interfering with viral multiplication. Upon clinical testing, however, only some of these appear to possess sufficient therapeutic effectiveness to recommend their use. The action mechanism of these, their possible side effects, the data proving their effectiveness and the main unsolved problems for their use are analysed.

Routine laboratory investigations performed on the serum of an 8-year-old girl examined because of a moderate degree of iron-deficiency anemia showed a markedly reduced C3 level. More detailed complement studies revealed a selective C3 deficiency, as indicated by the almost undetectable C3 concentration tested by both hemolytic and immunochemical assays and by the normal or slightly reduced levels of all the other complement components. The hemolytic activity of the serum was restored by the addition of partially purified C3 component. The isolated C3 deficiency could be attributed to the presence of a C3-cleaving activity in the serum of the propositus. This activity was identified as C3 nephritic factor (C3NeF) since it was heat-stable, was absorbed by Cowan I strain of Staphylococcus aureus and was-eluted in the IgG fraction after DEAE-chromatography of the serum. The levels of H and I factors of the alternative pathway in the serum of the propositus and of C3 in the serum samples of her parents and two siblings were found to be within the normal range. The previous clinical history of the girl and the follow-up for a period of approximately 5 years showed that she was apparently healthy and did not reveal clinical and/or laboratory evidence of glomerulonephritis, lipodystrophy or repeated bacterial infections usually associated with the presence of C3NeF in the serum.

The hemagglutinating activity of Sindbis virus on untreated or tripsinized blood red cells of some animal species was assessed. In some cases tripsinization increases the red cell sensitivity to viral hemagglutinin. Interferon (IFN) production induced by Sindbis virus on human WISH, mouse L-929 and chicken FEP cells was similar in all three cases. The effects of the temperature on virus replication were studied. Optimal growth was seem to take place at 37 degrees C. These data suggest that the viral pathogenic effect in humans in contrast to the asymptomatic infection in reservoirs is not related to differences in IFN production, but could be due to differences in host body temperature.

Peripheral blood lymphocytes (PBL) of 11 patients with CVI produced reduced levels of interleukin-4 (IL-4) upon activation by mitogens as compared with those secreted by PBL of healthy donors. The interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production by PBL of a series of 15 patients with CVI was also reduced. Decreased levels of IL-4 or IL-2 and IFN-gamma production were not only observed after activation by phytohaemagglutinin (PHA) at concentrations of 10 and 1 micrograms/ml, but also after activation by concanavalin A (Con A, 10 micrograms/ml). Longitudinal studies indicated that this defective lymphokine production was consistent upon testing periods up to 5 months. No correlation between reduced IL-4, IL-2 or IFN-gamma production was observed. PBL of patients that produced reduced levels of one lymphokine generally secreted normal levels of the other two lymphokines. Despite the reduced synthesis of the T cell growth factors IL-2 and IL-4, the proliferative responses of the PBL of the patients were in the normal range, which is compatible with the finding that IL-2 and IL-4 have synergistic effects on lymphocyte proliferation, particularly when one of these lymphokines is present at suboptimal concentrations. Since IL-2, IL-4 and IFN-gamma can act as B cell growth and differentiation factors, our data suggest that the reduced synthesis of these lymphokines may contribute to the deficient immunoglobulin production in patients with CVI.

T-cell phenotypic analysis with anti-T monoclonal antibodies (MoAb) was performed on 37 children with immunologic disorders. Abnormalities of T-cell differentiation and/or of T-cell subset distribution were observed in many patients. In particular two infants with severe combined immunodeficiency showed immunologically incompetent common thymocytes (OKT6+) in the circulation, in one case a proportion of OKT6+ cells was OKT4-, OKT8-. A boy with a selective T-cell defect synthetized normal levels of Ig classes, despite the marked reduction of helper/inducer T-cells (OKT4+). Irregularities of T-cell subsets were also noted in children with Wiskott-Aldrich syndrome and in some patients with selective IgA defect or hypogammaglobulinaemia. In one of these, in whom the agammaglobulinaemia was caused by EBV infection, a persistently reversed OKT4+/OKT8+ ratio together with an excessive suppressor T-cell function were found more than 10 years after the onset of the disease. Such a case supports the hypothesis that a viral infection may cause, in a predisposed host, both the agammaglobulinaemia and an abnormality of the regulatory T-cell subpopulations. Such abnormalities, together with those found in the other children studied, underline the importance of MoAb against different T-cell antigens for a better characterization of primary immunodeficiencies.

Virus induced interferon production has been studied in 21 children treated with Rifampicin, or Thiamphenicol or Prednisone . No significant difference has been observed before and after treatment in all but one patients.

The in vitro effect of different doses of alpha, beta and gamma human interferons and their interaction on the proliferation rate of human erythroleukemic cell line (K-562) and other cell lines has been evaluated. The results show that the stronger activity is exerted by beta HIF in comparison with alpha HIF. The action is selective and species-specific. beta HIF never elicited an "enhancing" effect on cell proliferation; on the contrary this phenomenon has been observed to occur with alpha and gamma HIF. In our cell system, the interaction between beta and gamma HIF gave a synergistic effect; on the contrary, no interaction has been observed to take place when beta HIF and directly cytotoxic mycotoxins extracted from A. terreus are associated.

IgG, IgA and IgM levels were studied in 187 homozygous beta-thalassemic patients and compared with age-matched normal control subjects. The not yet transfused and the polytransfused nonsplenectomized patients showed a significant increase of all Ig classes. The polytransfused splenectomized patients showed a significant increase only of IgG and IgA. The splenectomized patients, when compared to the nonsplenectomized ones, showed a significant increase of IgG, of IgA in the elder ones and a significant reduction of IgM. High ASLO and ASFLO titers were found especially in the splenectomized patients. The high Ig levels in younger not yet transfused patients, with little iron storage and normal hepatic enzyme values, demonstrate that transfusion therapy and liver damage do not play a main role in hypergammaglobulinemia. The absence of antimitochondrial, anticonnective tissue and homogeneous antinuclear antibodies seems to exclude a deficient suppressor mechanism. The hemocatheteric "overworking' of RES may reduce the antigen clearance with a consequent increase of antibody response. Splenectomy, by removing a consistent part of RES, enhances the phenomenon.

In the present study, we investigated the interleukin-2 (IL-2) production and the proliferative responses by peripheral blood mononuclear cells (PBMNC) of 23 children suffering from insulin-dependent diabetes mellitus (IDDM). In addition, the presence of circulating activated T lymphocytes expressing the interleukin-2 receptor (IL-2 R) and HLA-DR antigens was evaluated. The patients were tested at hospital admittance, before starting insulin treatment. Decreased IL-2 production by phytohemagglutinin (PHA)-activated PBMNC of IDDM patients was observed when compared to normal donors. In contrast, the proliferative responses of PBMNC to PHA and Con A were in the normal range. The expression of IL-2 R on patient's lymphocytes was not different from that observed in normal donors, whereas the relative and absolute number of HLA-DR+ T cells was increased. These results confirm the presence in IDDM patients of an imbalanced cellular immune response and demonstrate that the IL-2 deficiency is already present at the diagnosis and is not correlated with insulin administration.

Erythrocyte adenosine deaminase (ADA) activity was assessed in 33 children born to human immuno-deficiency virus (HIV)-positive mothers. The enzyme values were significantly increased in infected, symptom-free children compared with a control group of HIV-negative subjects (mean +/- SD: 0.34 +/- 0.01 unit/ml red blood cells (RBC) vs. 0.25 +/- 0.04 unit/ml RBC, P less than 0.01) and a further significant increase was found in symptomatic children (0.45 +/- 0.02 unit/ml RBC, P less than 0.01 vs. infected, symptom-free children). ADA values were slightly enhanced also in the group of infants in whom the state of HIV infection was indeterminate (0.29 +/- 0.03 unit/ml RBC, P not significant vs. controls). These data indicate that increased erythrocyte ADA activity may be a useful though indirect marker of HIV infection in children at risk and be of possible prognostic relevance. Since increased values were present also in children without overt infections or hematologic disorders, and ADA activity of erythrocytes obtained from healthy donors did not increase after 1 hour incubation with patients' serum, HIV could induce large amounts of cellular enzyme infecting directly erythroid precursor cells.

Four children with measles meningoencephalitis were treated with thymostimulin, a calf thymic extract. All patients were comatose when therapy was started. In all but one a good and sometimes rapid clinical improvement was observed. In the responsive patients no neurological or EEG sequellae were noted over a follow-up period of 1-4 years. The depression of cell-mediated immunity, present in some patients before treatment, normalised at the end of therapy.

Variation of serum immunoglobulin (Ig) levels and increased frequency of selective IgA deficiency are frequently associated with autoimmune diseases. In insulin-dependent diabetes mellitus (I.D.D.M.) pathogenesis autoimmunity is known to play a causative role. Aim of the present study was to evaluate serum major immunoglobulin subclasses levels and frequency of IgA selective deficiency in juvenile onset I.D.D.M. IgG, IgA, IgM concentrations were determined in 191 insulin-dependent children and adolescents (100 males, 91 females; mean age 10.6 divided by 4.8 yrs; mean duration of I.D.D.M. 5.7 divided by 3.9 yrs) and in 180 age-matched healthy controls. Mean Ig levels were comparable among both group. Duration of I.D.D.M. did not affect mean serum Ig levels. Selective IgA deficiency was found in 7 on 191 diabetics: this gives a prevalence of the defect of 1:27, which is higher than in the Italian pediatric population (1:500). HLA typing evidenced 2 DR3 positive patients, 2 DR4, 1 B8-DR3 and 1 B8-DR3/DR4. The significance of selective IgA deficiency in I.D.D.M. is discussed.

The histochemical NBT test was performed on blood samples from ten healthy newborn infants. High spontaneous NBT reduction has been confirmed for neutrophils and assessed for monocytes. The stimulation of both neutrophils and monocytes with Escherichia coli endotoxin induces a statistically significant increase of NBT positive cells. The reason for the false positive test results in neonates was investigated by incubating neutrophils from adult donors and for different time periods in either neonatal or adult plasma before the addition of NBT. NBT reduction by adult neutrophils was increased after incubation in neonatal plasma, and this increase was related to the concentration of the plasma used. Maximum NBT reduction was observed after 90 min of incubation, at which time the NBT scores of adult cells incubated in neonatal plasma were similar to the results of tests performed on whole neonatal blood. It is concluded that neonatal leucocytes demonstrate efficient spontaneous and stimulated phagocytosis, and that there are, in the plasma of neonates, humoral factors which stimulated phagocytosis by neutrophils and are thus responsible for the false positive NBT test results observed in these subjects.

Interferon-alpha and -gamma production was assayed in 44 children with recurrent respiratory tract infections, in 9 patients with recurrent stomatitis and in 32 control subjects. A partial, transitory deficiency in interferon-alpha production was found in 2 children with recurrent respiratory tract infections. The deficiency may be either cause or effect of the recurrent infections. Many data support the latter hypothesis.

Viral infections of the respiratory apparatus occur more frequently and their aetiology is often different, but there is no substantial difference between cases in children and in adults. Some clinical pictures, such as colds, laryngitis and bronchiolitis do, however, have an aetiology, symptomatology and course that deserves consideration. Features and diagnostic and therapeutic problems of these forms are analysed in brief.

We studied IFN inducing ability on syngenic C3H mice of a multibacterial antigenic extract consisting of different strains of following species: Staphylococcus aureus, Escherichia coli, Aerobacter aerogenes, Proteus vulgaris. A dose-dependent IFN production was demonstrated and two peaks of circulating IFN were observed few hours and two days after i.v. inoculation. Per os administration only at high doses induced evaluable levels of IFN in the circulation.

Beta-interferon was administered by intravenous infusion to 16 patients affected with fulminant hepatitis B virus infection in third or fourth-grade coma. Ten patients presented a superinfection or a co-infection due to the delta (delta)-agent. None had detectable interferon (IFN) activity before therapy was begun. Besides fever, no significant side-effects were observed during treatment. Both the IFN-treated group as well as the "historical" control group, made up of 70 cases of fulminant virus hepatitis, not treated with IFN and observed during a previous ten year-period, received supportive therapy; survival rates were similar in both groups. Furthermore, the presence or absence of the delta-agent did not appear to affect survival rates significantly.

Twenty-eight infants with bronchiolitis were randomized divided into two groups. Clinical diagnosis was made by scores indicated by the Bronchopneumology Study Laziale. Group one received thymostimulin (TP-1 Serono: 1.5 mg/kg/die for five days), while in the second group it was not administered. Interferon concentration in frozen serum (-20 degrees C) was evaluated at entry and after 48 hours. Etiology, severity grade and clinical characteristic were similar in both groups; this has made reliable the present evaluation. Although, in the first four days clinical score was slightly lower in the first group than in the second, there were not observed differences with statistics significance and hospitalization was similar in both groups. Because there has been described in literature an increase in interferon's production after TP-1 administration we evaluated the influence of this hormone on interferon's production. There were no differences with statistics significance with or without treatment. This study has not showed an important TP-1's efficiency in the treatment of bronchiolitis.

An infant with partial trisomy 22 syndrome and recurrent infections showed severe cellular immunodeficiency and serum IgG reduction. A marked increase of E-RFCs was observed after in vitro incubation of peripheral blood lymphocytes with thymostimulin (TS), a calf thymic extract. The treatment with TS resulted in reduction of infections, correction of cellular immunodeficiency and increase of IgG levels. Such a primary thymic hormone dependent immunodeficiency may be due to an altered development of branchial arches, commonly present in trisomy 22 syndrome. The same pathogenetic mechanism may account for thymus dysplasia observed in other chromosomal syndromes.

An 18-month-old girl with AIDS related complex following congenital HIV infection suffered since the first days of life from severe neurological disturbances. The extensive congenital brain atrophy and the diffuse intracranial calcification which were found were strongly reminiscent of intrauterine infection. Since the agents usually responsible for congenital infections were excluded an HIV embryopathy appears likely.

The in vitro effect of a calf thymus extract (TP-1) on peripheral blood lymphocytes was evaluated in sixty-six melanoma patients. Twenty out of forty-five stage I and seventeen out of twenty-one stage IIb patients presented depressed T lymphocyte values. A statistically significant increase in E-rosette-forming cells (E-RFC) was observed in seventeen (85%) stage I and twelve (70.5%) stage II patients. In thirteen (65%) stage I and eight (47%) stage II patients E-RFC reached normal values. Our results indicate that the fall of T lymphocytes in the peripheral blood of melanoma patients is often related to an increase in TP-1 sensitive cells which suggests the possibility of a thymic hormone deficiency in these patients.