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Immunotherapy units: a follow-up study.

Immunotherapy units are becoming an increasingly important component of allergy and clinical immunology departments in Spain. The objective of this study was to establish the rate of adverse reactions registered in an immunotherapy unit in Tenerife, Canary Islands, Spain, from May 1998 to May 2000. A total of 5,108 immunotherapy doses were administered to 339 patients (123 males and 216 females): 254 patients (75%) received mite, 48 patients (14.1%) pollen, 7 patients (2%) cat, 2 patients (0.6%) Alternaria alternata, and 38 patients (11.2%) hymenoptera venom immunotherapy; 238 patients (70.2%) had rhinoconjunctivitis and asthma, 59 (17.4%) rhinoconjunctivitis, 5 (1.4%) asthma, and 38 (11.2) hymenoptera sensitivity. A total of 42 episodes of adverse reactions were recorded (0.8% of all the administered doses). Of these reactions, 36 (85.7%) occurred within 30 minutes after the injection was administered, consisting of 15 large local reactions (0.3% of the total amount of injection given) and 21 systemic reactions (0.4%) that occurred only in asthmatic patients. All the systemic reactions were mild and rapidly reversible with appropriate treatment. Only in two cases was an immediate systemic reaction associated with a large local reaction. Six reactions (14.3%) occurred after 30 minutes and consisted only of large local reactions. A total of 15 systemic episodes (71.4% of all the systemic reactions) were registered at initial build-up doses. As to the types of allergens, 14.2% of the individuals receiving cat immunotherapy, 7.8% of the individuals receiving hymenoptera venom, 6.3% of the individuals receiving pollen immunotherapy, and 2.7% of the individuals receiving mite immunotherapy experienced an adverse reaction. Only 0.8% of the administered doses presented any kind of adverse reaction, of which only 0.4% were systemic. The latter were always mild and rapidly reversible with adequate treatment, and there was no vital danger for any patient. Immunotherapy is a safe modality of treatment for allergic respiratory diseases and immunotherapy units provide a controlled and safe environment for its administration.

Adolescent↗

The effect of house dust mite specific immunotherapy on cysteinyl leukotriene production by blood leukocytes in subjects with perennial allergic rhinitis and asthma.

Specific immunotherapy has been successfully used in the treatment of allergic diseases for years. In this study, we examined the clinical efficacy of specific immunotherapy and its effect on cysteinyl leukotriene releasability by blood leukocytes in house dust mite allergic subjects with asthma and allergic rhinitis. In an open, parallel study, 13 subjects were treated with specific immunotherapy for 12 months and five patients served as the control group. Before specific immunotherapy treatment, and 1 and 12 months after, patients were evaluated with respect to total immunoglobulin (Ig) E levels, Dermatophagoides pteronyssinus specific IgE levels, symptom scores, usage of rescue medicines, lung function tests, nasal challenge scores, skin reactivity to D. pteronyssinus and cysteinyl leukotriene releasability by blood leukocytes. At the 12th month of specific immunotherapy, total asthma symptom scores, bronchodilator requirement, number of sneezes following nasal challenge and immediate skin reactivity to D. pteronyssinus was decreased, while FEV1 increased compared to the pretreatment values (p < 0.05 for each). These parameters remained unchanged in the control group. In vitro cysteinyl leukotriene releasability by blood leukocytes in response to D. pteronyssinus antigen and anti-IgE antibody remained unchanged both in the specific immunotherapy group and the control group. However, in the treated group, there were six patients who showed at least a 50% reduction in their symptoms after specific immunotherapy. In five of these, cysteinyl leukotriene release induced by both HACM buffer and D. pteronyssinus were decreased by more than 50% of the baseline values. The other patient demonstrated only a marked decrease (more than 50%) in background. Our results suggest that specific immunotherapy is effective in the treatment of allergic rhinitis and bronchial asthma due to house dust mite allergy and that the clinical response to specific immunotherapy may be associated with decreased cysteinyl leukotriene releasibility by blood leukocytes in some patients.

Adolescent↗

[Cancer immunotherapy. A future therapeutical choice?].

The idea that there might be an immune response to cancer has been around for many years. Immunotherapy has a long history, but is only rarely considered as the treatment of choice. Immunotherapy has encountered a number of intrinsic difficulties in cancer, such as the antigenic resemblance between the tumour and normal cells, the rapid kinetic proliferation of tumour cells and their reduced immunogenicity. There are various types of immunotherapy. Aspecific immunotherapy augments the body s immune response without targeting specific tumoral antigens. In adoptive immunotherapy, cells are administered with antitumoral reactivity to mediate neoplasm regression. Specific active immunotherapy is based on the principle that neoplasm cells contain immunogenic sites against which an antitumoral immune response can be induced in an attempt to stimulate the immune system to target specific tumoral antigens. Vaccines against cancer cells are based on a more precise identification of the tumoral antigen components. Passive immunotherapy was limited by the difficulty of obtaining high titering and specificity in early attempts using polyclonal antisera; monoclonal antibodies are currently used alone or in association with radioactive substances and cytotoxic agents. Enormous progress has been made this century in the use of immunotherapy for cancer treatment. It seems likely that the next century will see its increased afficacy, making it one of the possible therapeutic options.

Antibodies, Monoclonal↗

Stinging insect allergy: natural history and modification with venom immunotherapy.

The natural history of stinging insect allergy and its modification by venom immunotherapy was investigated by follow-up observations of patients with histories of venom anaphylaxis and detectable venom-specific IgE. The patients were divided into three categories: (1) receiving venom immunotherapy, (2) declined venom immunotherapy, and (3) terminated venom immunotherapy. One hundred twenty-seven patients were evaluated after 6 mo to 9 yr of venom immunotherapy. Most received top venom doses of 50 micrograms of yellow jacket and/or honeybee venoms every 4 wk. There were 87 restings in 48 patients resulting in two systemic reactions, only one of which could be considered a treatment failure (1%). Fifty-six patients never received venom immunotherapy. In this group there were 40 restings in 28 patients with 14 systemic reactions (35%). In 88 patients who stopped venom immunotherapy, 61 restings in 41 patients led to 11 systemic reactions (17%). Patients with cardiovascular/or respiratory symptoms with initial sting anaphylaxis were at risk for subsequent reactions. With one exception, patients with hives and edema only as the initial reaction either had a similar or no reaction when they were restung. These results confirm the efficacy of venom immunotherapy but also suggest that there are factors other than the presence of venom-specific IgE modulating the occurrence of clinical anaphylaxis.

Adolescent↗

Common cancers--immunotherapy and multidisciplinary therapy: Parts III and IV.

The refractoriness of many solid tumors to cytotoxic chemotherapy has led to the exploration of new therapeutic modalities, including immunotherapy. Immunotherapy does not have a direct cytotoxic effect on the cancer cell but is an attempt to promote rejection of the tumor by the host, chiefly through the cellular arm of the immune system. The clinical success with immunotherapy (primarily adoptive immunotherapy) among patients with unresectable malignant melanoma and cancer of the kidney has not been marked by the large numbers of patients responding but by occasional dramatic effectiveness of therapy for these cancers, which usually are refractory to chemotherapy. Long-lasting responses and even complete disappearance of all known metastases are possible for a small percentage of patients with melanoma or renal cell carcinoma who undergo immunotherapy. A reasonable approach for patients with good performance status (no symptoms or ambulatory with symptoms but not bedridden) is entrance to clinical trials, especially trials examining adoptive or active immunotherapy for melanoma or adoptive immunotherapy for renal cancer. The overall treatment of patients with cancer has changed. Primary-care physicians detect almost all cancers. The days when "taking it out" is the best we could offer a patient are over. As we learn more about the use of adjuvant or neoadjuvant chemotherapy and radiation therapy, it is likely one or both of these modalities will be incorporated into the treatment of additional solid tumors previously managed solely with surgical resection. Increasingly, additional therapy is being given for earlier-stage disease as we define how to maximize the potential for cure with minimal toxicity. Many new therapies are on the horizon, including the use of noncytotoxic treatments as an adjunct to a surgical procedure. Such therapies include the use of angiogenesis inhibitors, tumor vaccines, and immunotherapy. Now and in the future, patients will be best served when treated in an environment that can integrate medical, surgical, and radiation oncology actively.

Breast Neoplasms↗

Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom.

BACKGROUND: Specific immunotherapy with honeybee venom (BV) is highly effective, but allergic side effects can occur during treatment. Immunotherapy with peptides containing major T-cell epitopes of the relevant allergen or allergens provides an alternative strategy without these problems. OBJECTIVE: The study investigates the immunologic mechanisms and clinical effects of immunotherapy with T-cell epitope peptides of the major BV allergen, the phospholipase A2 (PLA). METHODS: Five patients with IgE-mediated systemic allergic reactions to bee stings were treated with a mixture of three T-cell epitope peptides of PLA. Ten patients allergic to BV receiving whole BV immunotherapy served as control subjects. Increasing doses of the peptide mixture, up to a maintenance dose of 100 microg, were administered subcutaneously within 2 months. The patients were then challenged with PLA and 1 week later with a bee sting. The cellular and humoral immune response was measured in vitro. RESULTS: No allergic side effects were caused by the peptide immunotherapy, and all patients tolerated the challenge with PLA without systemic allergic symptoms. Two patients developed mild systemic allergic reactions after the bee sting challenge. After peptide immunotherapy, specific proliferative responses to PLA and the peptides in peripheral blood mononuclear cells were decreased in successfully treated patients. The production of TH2 and TH1 cytokines was inhibited, and B cells were not affected in their capacity to produce specific IgE and IgG4 antibodies. Their levels increased after allergen challenge in favor of IgG4. CONCLUSIONS: Immunotherapy of BV allergy with short T-cell peptides of PLA induces epitope-specific anergy in peripheral T cells and changes the specific isotype ratio in a fashion similar to that of conventional immunotherapy in successfully treated patients.

Adolescent↗

Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms.

Immunotherapy with interferon-alpha (IFNalpha) may induce depressive symptoms, anxiety and major depression when administered for at least 1-3 months at a dose of 3-10 MUI daily, twice or three times a week. Previously, it has been shown that immunotherapy with interleukin-2 (IL-2) significantly induces the cytokine network, as measured by increases in serum IL-6, IL-10 and the IL-2 receptor (IL-2R), and that the immunotherapy-induced changes in the cytokine network are significantly correlated with the increases in depression ratings. The main aim of this study was to examine the effects of immunotherapy with IFNalpha on the cytokine network in relation to changes in depression and anxiety ratings. Fourteen patients, affected by chronic active C-hepatitis, were treated with IFNalpha (3-6 MUI s.c. three/six times a week for 6 months) and had measurements of serum IFN-gamma (IFNgamma), IL-2, IL-6, IL-6R, IL-8 and IL-10 before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNalpha. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Repeated measure (RM) design ANOVAs showed significantly higher MADRS and HAM-A scores 2-4 weeks and 4-6 months after starting IFNalpha-based immunotherapy than at baseline. RM design ANOVAs showed significantly higher serum IL-6 and IL-8 levels 2-4 weeks after starting IFNalpha-based immunotherapy and higher serum IL-10 levels 2-4 weeks and 4-6 months after starting therapy than at baseline. There were significant relationships between the IFNalpha-induced changes in serum IL-6 or IL-8 and the depression and anxiety scores. The findings show that IFNalpha-based immunotherapy induces the cytokine network and that IFNalpha-induced increases in IL-6 predicts the development of depressive symptoms. Depressive symptoms following IFNalpha treatment may be secondary to cytokine induction, including that of IL-6.

Adult↗

DNA-based immunotherapy to treat atopic disease.

OBJECTIVE: To review the current literature regarding DNA-based immunotherapy with respect to signaling mechanisms, cytokine profiles, and the applicability and success of this strategy to treat allergic disease. DATA SOURCES: English-language articles were identified from the PubMed database using both standard and clinical queries. Search terms included CpG, allergy, atopic disease, immunotherapy, DNA vaccination, immunomodulation, and immunostimulatory DNA. Other sources included bibliographies from relevant articles. STUDY SELECTION: Recent studies that provide information about the mechanisms or applications of DNA-based immunotherapy with respect to atopic disease are included in this review. RESULTS: DNA-based immunotherapy composed of unmethylated CpG repeats is capable of inducing a shift in the cytokine profile and immune response that favors the T(H)1 arm. This observation makes DNA-based immunotherapy a promising candidate for the treatment of atopic diseases, which are known to be mediated by T(H)2-based responses. Early animal and human trials of DNA-based immunotherapy have shown the strategy to be both safe and effective. CONCLUSIONS: DNA-based immunotherapy, although still in the early stages of development, has thus far been shown to be both safe and effective for a variety of atopic diseases and offers the potential for significant improvements over current immunotherapy protocols.

Animals↗

Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma--a placebo controlled study.

BACKGROUND: The efficacy of therapy with sublingual allergen extracts is unproven. OBJECTIVE: To evaluate the clinical and immunologic outcome of sublingual immunotherapy and to compare the results with subcutaneous immunotherapy and placebo in 36 patients with rhinitis and asthma due to mite allergy. METHOD: Thirty-six patients with rhinitis and asthma due to mite allergy were randomly divided into three groups in order to receive subcutaneous injections with allergenic extracts, sublingual drops with solutions of purified standardized allergen preparations, or sublingual placebo for a period of 1 year. Assessment of clinical and immunologic efficacy included symptom and medication scores, methacholine provocation tests, skin prick tests, and specific IgE and IgG4 antibody concentrations. RESULTS: Subcutaneous immunotherapy for both rhinitis and asthma was clinically effective. Patients treated with sublingual immunotherapy had decreased rhinitis symptoms (P < .01) but no change in asthma scores. Medication scores significantly decreased in both actively treated groups (P < .01) at the first year compared with baseline. When skin prick tests were evaluated, the subcutaneously treated group had a significant decrease in the wheal diameter of D. pteronyssinus (P < .01), D. farinae (P < .05), and histamine (P < .05) while other two groups showed no difference. There was no significant change in methacholine PC20 values in all groups at the end of the first year when compared with baseline. No change in D. pteronyssinus and D. farinae specific IgE levels were observed; however, specific IgG4 concentrations were significantly higher than baseline both in sublingual and subcutaneous immunotherapy groups (P < .05) after 1 year immunotherapy. No significant difference was obtained in any of these parameters in the placebo group. CONCLUSION: Sublingual immunotherapy may be effective in patients with allergic rhinitis. Further, we believe it is a potential therapy for allergic asthmatic patients. The clinical usefulness of this form of immunotherapy (when administered to larger study groups for a longer time) and the mechanisms underlying its immunologic effect deserve additional studies.

Administration, Cutaneous↗

Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma.

Immunotherapy is the only available treatment for metastatic renal cell cancer (RCC), but the response rate is only about 20% and the treatment is occasionally associated with severe adverse effects. Thus, the selection of patients with a high susceptibility to immunotherapy is needed; however, there is no promising molecular marker that can predict the response to immunotherapy for RCC. This study was carried out to elucidate the potential role of apoptosis-related molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI) as predictors of the susceptibility of metastatic RCC to immunotherapy. Immunohistochemical examination of tumour tissues from 40 patients with metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy was performed. Patients with progressive disease (PD) after immunotherapy presented with decreased survival (P=0.006). Progressive disease correlated with higher PI in the primary lesion (P=0.0087). All primary tumours of CR or PR patients were negative for Bcl-2, whereas among NC+PD patients, 40.6% were positive for Bcl-2 (P=0.0373). Patients in whom the primary tumours were both Bcl-2- and Fas-negative showed significantly better responses to immunotherapy in comparison with the remaining group (P=0.0022). The Bcl-2 and Fas status of the primary lesion may become useful criteria for the selection of patients with metastatic RCC for immunotherapy.

Adult↗

The clinical role of specific IgE and IgG4 antibodies in patients having immunotherapy for seasonal allergic rhinitis.

This study was designed to investigate the clinical role of specific IgG4 and IgE responses in patients during immunotherapy for seasonal allergy. The study included 109 patients with seasonal allergic rhinitis due to Japanese cedar pollens. They were divided into the control group and the immunotherapy group. Serum samples were obtained at the start of immunotherapy, before the pollen season and during the season, to determine serum specific IgE and IgG4. In the control group specific IgE was significantly increased, but specific IgG4 was not changed during the pollen season. In the immunotherapy group specific IgE was not significantly increased, but specific IgG4 was significantly increased during the season. In the patients having immunotherapy for 2 years or less, the seasonal increase in specific IgG4 related to the magnitude of the clinical effect. In the patients having immunotherapy for 3 years or more, the seasonal increase in specific IgE related to the magnitude of the clinical effect. In conclusion, the specific IgG4 response and specific IgE response during the pollen season make a significant contribution to the clinical effect of immunotherapy. However, modulation of specific IgE and IgG4 responses out of the pollen season was unlikely to be an important phenomenon related to the clinical effect of immunotherapy.

Adolescent↗

Ten-year follow-up study of allergen-specific immunoglobulin E and immunoglobulin G4, soluble interleukin-2 receptor, interleukin-4, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in serum of patients on immunotherapy for perennial allergic rhinitis.

Recent double-blind placebo-controlled trials for perennial allergic rhinitis have all clearly shown the efficacy of immunotherapy. Although several mechanisms for the clinical efficacy of immunotherapy have been proposed, the exact mechanisms related to the clinical effect still remain unclear. Since immunotherapy is a form of systemic treatment and its clinical benefit is likely to be, at least in part, a consequence of its systemic effects on different phases of immunological events, our study focused exclusively on several immunological parameters in serum. A total of 47 patients with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective study. Venous blood was collected for determination of specific immunoglobulin (Ig)E, specific IgG4, soluble interleukin-2 receptor (IL-2R), interleukin-4 (IL-4), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1), six times from 20 untreated patients and 27 patients on immunotherapy, at enrolment, and 1, 2, 3, 5, and 10 years after enrollment. No specific IgE, IgG4, soluble IL-2R, IL-4 and soluble ICAM-1 levels changed significantly for a span of 10 years in the untreated patients. By contrast, immunotherapy affected serum levels of specific IgE, specific IgG4, soluble IL-2R, IL-4 and soluble ICAM-1, but not of soluble VCAM-1. The rates of increase in specific IgG4 and the rates of decrease in soluble IL-2R were correlated with the rates of decrease in symptom scores during the first 3 years, but not 5 and 10 years after the course of immunotherapy. On the other hand, the rates of decrease in specific IgE, IL-4 and soluble ICAM-1 were significantly correlated with the rates of decrease in symptom scores at 5 and 10 years, but not during the first 3 years. Each immunological modulation by immunotherapy was likely to be involved in the working mechanism related to clinical efficacy at different phases of immunotherapy.

Adolescent↗

Suppression of seasonal increase in serum interleukin-5 is linked to the clinical efficacy of immunotherapy for seasonal allergic rhinitis.

Although immunotherapy is recognized as a highly effective form of treatment for allergic rhinitis, especially pollen-induced seasonal allergic rhinitis, the mechanisms have not been fully established. In the present study, we investigated whether immunotherapy could affect the seasonal increase in interleukin-5 (IL-5) in the serum of patients with seasonal allergic rhinitis and whether the effect on IL-5 in serum is related to the clinical efficacy of immunotherapy. Venous blood was collected twice from each patient with seasonal allergic rhinitis due to Japanese cedar pollens, before and during the cedar pollen season in 1997, to determine the cedar pollen-specific IgE and IL-5 in serum. Both specific IgE and IL-5 in serum were significantly increased during the pollen season, not only in the poor responders to antihistamines but also in the good responders. Neither the rate of seasonal increase in specific IgE nor the rate of seasonal increase in IL-5 differed significantly between the good responders and the poor responders to antihistamines. Both specific IgE and IL-5 were significantly increased during the pollen season in the poor responders to immunotherapy, whereas neither specific IgE nor IL-5 was increased during the pollen season in the good responders to immunotherapy. The rate of seasonal increase in specific IgE as well as IL-5 was significantly smaller in the good responders than in the poor responders to immunotherapy. The rates of seasonal increase in specific IgE and in IL-5 were inversely correlated with the length of time on immunotherapy. However, the rate of seasonal increase in specific IgE was not significantly correlated with the rate of seasonal increase in IL-5. In conclusion, the suppression of the seasonal increase in IL-5 in serum is a working mechanism of immunotherapy related to the clinical efficacy of the treatment.

Adult↗

Immunotherapy: an option in the management of occupational asthma?

PURPOSE OF REVIEW: To review clinical data on immunotherapy applied to occupational asthma. RECENT FINDINGS: There are very few studies on immunotherapy in occupational asthma. The best documented use of immunotherapy in this disorder corresponds to latex allergy among healthcare workers. There are anecdotic reports of non-well controlled studies using immunotherapy with wheat flour, African maple wood, sea squirt and rat epithelium extracts. Subcutaneous immunotherapy with natural rubber latex extract, at adequate doses, seems to be a useful treatment in reducing cutaneous and respiratory symptoms, but it should be considered as a high-risk treatment due to the appearance of systemic reactions. SUMMARY: At present, subcutaneous immunotherapy with latex extract can only be considered experimental and must be administered by experienced allergists in a hospital setting, similarly to venom immunotherapy. Nevertheless, systemic reactions responded well to treatment. Further clinical trials on efficacy, safety and long-term effectiveness in immunoglobulin E-mediated occupational rhinitis and asthma are clearly needed. Since allergen avoidance is not always possible, no other etiologic treatment but immunotherapy can be offered to patients with occupational rhinitis/asthma.

Animals↗

Is allergen immunotherapy effective in asthma? A meta-analysis of randomized controlled trials.

A meta-analysis of clinical trials of allergen immunotherapy was undertaken to assess the efficacy of this controversial form of therapy in asthma. A computerized bibliographic search revealed 20 randomized placebo controlled double-blind trials of allergen immunotherapy for asthma. The results extracted included asthmatic symptoms, medication requirements, lung function, and bronchial hyperreactivity (BHR). Categorical outcomes were expressed as odds ratios and continuous outcomes as effect sizes. The combined odds of symptomatic improvement from immunotherapy with any allergen were 3.2 (95% CI 2.2 to 4.9). The odds for reduction in medication after mite immunotherapy were 4.2 (95% CI 2.2 to 7.9). The combined odds for reduction in BHR were 6.8 (95% CI 3.8 to 12.0). The mean effect size for any allergen immunotherapy on all continuous outcomes was 0.71 (95% CI 0.43 to 1.00), which would correspond to a mean 7.1% predicted improvement in FEV1 from immunotherapy. Although the benefits of allergen immunotherapy could be overestimated because of unpublished negative studies, an additional 33 such studies would be necessary to overturn these results. Allergen immunotherapy is a treatment option in highly selected patients with extrinsic ("allergic") asthma.

Asthma↗

Opposite effects of immunotherapy with ovalbumin and the immunodominant T-cell epitope on airway eosinophilia and hyperresponsiveness in a murine model of allergic asthma.

In the present study, we investigated immunotherapy using an entire protein or an immunodominant epitope in a murine model of allergic asthma. Immunotherapy was performed in ovalbumin (OVA)-sensitized mice before OVA challenge. Mice were treated subcutaneously with OVA, the immunodominant epitope OVA323-339, or vehicle. In vehicle-treated animals, repeated OVA challenge induced increased serum levels of OVA-specific immunoglobulin (Ig)G1, IgE, airway eosinophilia, and hyperresponsiveness, compared with saline-challenged animals. In addition, interleukin (IL)-4 and IL-5 production upon OVA restimulation of lung-draining lymph node cells in vitro were significantly increased in OVA-challenged animals. Immunotherapy using OVA significantly reduced airway eosinophilia and hyperresponsiveness. This finding was accompanied by significantly reduced OVA-specific IL-4 and IL-5 production. Further, OVA immunotherapy induced increased serum levels of OVA-specific IgG1, whereas OVA-specific IgG2a and IgE levels were not affected. In contrast to OVA immunotherapy, immunotherapy with OVA323-339 aggravated airway eosinophilia and hyperresponsiveness. OVA-specific IgG1, IgG2a, and IgE serum levels, and in vitro IL-4 and IL-5 production, were not affected. Thus, immunotherapy with protein resulted in beneficial effects on airway eosinophilia and hyperresponsiveness, which coincided with a local reduced T-helper 2 (Th2) response. In contrast, peptide immunotherapy aggravated airway hyperresponsiveness and eosinophilia, indicating a local enhanced Th2 response.

Animals↗

[Active immunotherapy of acute leukemia and leukemic lymphosarcoma. Results of 10 years. Study of 200 cases].

The authors report a ten year study of active immunotherapy using BCG and irradiated allogeneic leukaemic cells in 200 patients. In acute lymphatic leukaemia, 57 out of 168 patients treated in this way remained in primary remission for 18 months to 10 years after active immunotherapy was begun, the relapse rate became low after 18 months and nil after 36 months. The results varied according to prognostic factors: the cytological type, active immunotherapy being above all effective in small cell (microlymphoblastic and prolymphocytic) types with a hope of cure in 50 to 60 p.cent of cases; malignant cellular volume; meningeal deposits. In microlymphoblastic forms the possibility of survival at the 5th year is greater than 90 p.cent. After relapse during active immunotherapy sensitivity to chemotherapy does not seem to be diminished. Trials of active immunotherapy in acute myeloid leukaemia are worthy of further pursuit. The results of active immunotherapy in leukaemic lymphosarcoma show that immunotherapy may be effective in preventing local recurrence, both of tumour as well as in the marrow. Four patients are in apparently complete remission for more than four years. On the basis of these results, trials of active immunotherapy for "residual disease" should be undertaken in the field of cancerology, going beyond the realm of leukaemias.

Adjuvants, Immunologic↗

[Clinical efficacy of immunotherapy with house dust in the patients with perennial nasal allergy].

We tried to elucidate the relation of age and severity with the efficacy of immunotherapy. The subjects included 51 patients with perennial allergic rhinitis who had immunotherapy for more than a year. Symptom scores, serum total IgE levels, Dermatophagoides pteronyssinus specific IgE, and peripheral blood eosinophils counts were evaluated before, half a year, one year and two years after the onset of immunotherapy. 64% of the children's group and 69% of the adults' group of patients showed significant improvement in their nasal symptoms, showing that age is not a factor influencing the efficacy of immunotherapy. The severity of the disease influenced the clinical efficacy; the more severe the disease, the poorer the efficacy of the immunotherapy. Periphipheral blood eosinophils counts gradually decreased after the onset of immunotherapy. High eosinophil counts before immunotherapy predicted poor efficacy of the immunotherapy.

Adolescent↗