Fig (Ficus carica L.) leaf tea suppresses allergy by acceleration disassembly of IgE-receptor complexes.

In this study, I investigated the allergy suppressive effect of tea made from fig (Ficus carica L.) leaves. In the rat basophil cell line RBL-2H3, degranulation was significantly suppressed by treatment with fig tea at the same time as addition of IgE antibodies (sensitization). IgE bound to the cell surface was liberated in the medium depending on the treatment time with fig tea. Therefore, it was suggested that the mechanism of action of fig tea is promotion of dissociation of IgE from FcεRI receptors. Such a mechanism is novel in food materials. On oral administration to mice, fig tea showed an inhibitory effect on allergic dermatitis. Furthermore, in tests using an atopic dermatitis model in NC/Nga mice, continued administration of fig tea suppressed symptom exacerbation after antigen administration.Abbreviations: AD: atopic dermatitis; ß-Hex: ß-hexosaminidase; FCM: flow cytometory; OA: oral administration; TA: transdermal administration.

A Proliferation Inducing Ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy.

IgA nephropathy (IgAN) is the most prevalent primary chronic glomerular disease for which no safe disease-specific therapies currently exist. IgAN is an autoimmune disease involving the production of autoantigenic, aberrantly O-glycosylated IgA1 and ensuing deposition of nephritogenic immune complexes in the kidney. A Proliferation Inducing Ligand (APRIL) has emerged as a key B-cell-modulating factor in this pathogenesis. Using a mouse anti-APRIL monoclonal antibody (4540), we confirm both the pathogenic role of APRIL in IgAN and the therapeutic efficacy of antibody-directed neutralization of APRIL in the grouped mouse ddY disease model. Treatment with 4540 directly translated to a reduction in relevant pathogenic mechanisms including suppressed serum IgA levels, reduced circulating immune complexes, significantly lower kidney deposits of IgA, IgG and C3, and suppression of proteinuria compared to mice receiving vehicle or isotype control antibodies. Furthermore, we translated these findings to the pharmacological characterization of VIS649, a highly potent, humanized IgG2κ antibody targeting and neutralizing human APRIL through unique epitope engagement, leading to inhibition of APRIL-mediated B-cell activities. VIS649 treatment of non-human primates showed dose-dependent reduction of serum IgA levels of up to 70%. A reduction of IgA+, IgM+, and IgG+ B cells was noted in the gut-associated mucosa of VIS649-treated animals. Population-based modeling predicted a favorable therapeutic dosing profile for subcutaneous administration of VIS649 in the clinical setting. Thus, our data highlight the potential therapeutic benefit of VIS649 for the treatment of IgAN.

Drug evaluation: the C5a receptor antagonist PMX-53.

Peptech is developing PMX-53, a complement C5a inhibitor for the potential treatment of inflammatory disorders, including rheumatoid arthritis and psoriasis. Phase Ib/IIa clinical trials have been completed for both indications.

Antibodies to delta sleep-inducing peptide in ultralow doses: study of the effect by enzyme immunoassay.

The effects of potentiated homeopathic preparations containing antibodies to delta sleep-inducing peptide in ultralow doses were studied by enzyme immunoassay. Experiments were performed with the following immunochemical reagents: antigens of delta sleep-inducing peptide conjugated to various macromolecular carriers and specific antigens. Antibodies to delta sleep-inducing peptide were synthesized in dilutions of C3, C6, C12, C50, and C200. Enzyme immunoassay showed that test preparations of antibodies in dilutions of 1:400-1:3200 produce the combined effect on immune complex formation. The proposed method holds much promise for identification of medicinal preparations in ultralow doses.

Considerations relating to the epidemiology of human immunodeficiency virus infection: the impact of bacterial antigens and consequences for treatment.

OBJECTIVE: A treatment for patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is presented, which is based on an isopathic method that appears to be effective in eliminating bacterial antigens from the body. The concept is based on a new hypothesis concerning the outbreak and spread of AIDS in Africa and worldwide. SUBJECTS AND DESIGN: Laboratory data are presented from five European and seven African patients with HIV. RESULTS: Oral administration of ultra-low doses of a lysate of Staphylococcus aureus Cowan I (12c potency) resulted in a significant increase of CD4 T-cell subsets and CD4/CD8 ratios in patients with HIV infection as well as in advanced stages of HIV disease, concomitant with the improvement of clinical HIV-related symptoms. CONCLUSIONS: Based on epidemiologic data, the beginning of the African AIDS epidemic is related-to time, place, and circumstances-to the initial large-scale introduction of antibiotics in areas of Central Africa that would later comprise the AIDS belt. It is concluded that certain antimicrobial agents can enhance the formation of persistent bacterial superantigens, which may indicate a link between asymptomatic HIV carriers and the development of AIDS. According to this view, superantigens and bacterial cell wall components remaining in the body after antibiotic treatment cause a permanent activation of the immune system and would thus favor T-cell infection and viral replication in HIV-infected individuals.

Immunologic changes in healthy probands and HIV infected patients after oral administration of Staphylococcus aureus 12c: a pilot study.

The tumoricidal and antiviral effects of Staphylococcal toxins are well documented. In a preliminary study we investigated the immune modulating properties of these toxins by administering single oral doses of a 12c potency of a lysate of Staphylococcus aureus Cowan I, to 4 healthy probands and 12 HIV infected patients with clinical symptoms. We observed a decrease of circulating immune complexes in the healthy probands as well as in the HIV positive patients, accompanied in the latter by a significant increase of CD4 lymphocytes, CD4/CD8-ratio and an improvement of the HIV related symptoms. None of the dose dependent toxic effects commonly found in Staphylococcal sepsis were noticed. Further research on the immune modulating effects of potencies of bacterial superantigens is suggested, especially in view of a possible treatment for HIV infected and other immune compromised patients.

Association of immunological changes with clinical efficacy in atopic eczema patients treated with traditional Chinese herbal therapy (Zemaphyte).

The efficacy of the Chinese herbal therapy (Zemaphyte) has been well established as a treatment for atopic eczema (AE) in clinical trials. The purpose of this study was to probe the immunological changes that occurred when patients were treated with the herbs for a period of 8 weeks. This treatment decreased serum IgE complexes (p less than 0.05) but did not affect total serum IgE or CD23 expression on peripheral blood monocytes. Peripheral blood mononuclear cells from patients before and after treatment were cultured overnight with interleukin 4 and the ability of this cytokine to induce CD23 on monocytes from treated patients was found to be significantly diminished (p less than 0.01). Soluble interleukin 2 receptor and soluble vascular cell adhesion molecule were both raised in the serum of AE patients compared to control individuals. Both these parameters were decreased following treatment (p less than 0.05). All these changes coincided with improvement in erythema and surface damage scores. There was no alteration in soluble intracellular adhesion molecule or soluble CD23. The results of these investigations would suggest that this herbal treatment has the ability to target various immunological parameters which may be involved in the pathogenesis of AE.

Effects of Kampo medicines on the clearance of circulating immune complexes in mice.

Toki-Shakuyaku-san (TSS), a Japanese (Kampo) formulation which consists of six herbs, was administered orally to MRL Mp-lpr/lpr mice for 6 weeks. Clearance was measured by in vivo enzymatic immune complex clearance (EIC) assay. Glucose oxidase-anti-glucose-oxidase complexes (GAG), as a model of immune complexes (ICs), was injected into mouse tail veins and at intervals thereafter the enzyme activity of the GAG remaining in the circulation were estimated. The half life (T1/2) of GAG from the circulation was significantly shortened in the TSS-treated group. Furthermore, the amount of circulating immune complexes, measured by anti-mouse C3 ELISA, tended to decrease in the TSS-treated group. We also evaluated three other Kampo formulas, but no significant effect was observed for these formulations. We then examined the activity of the individual herbs in TSS and in formulations excluding one component herb. No significant changes were observed with individual herbs. On the other hand, the activity observed in the TSS-treated group disappeared in the TSS minus Angelicae Radix formulation and the TSS minus Atractylodis Lanceae Rhizoma formulation. These observations indicate that TSS is a potent formula and its enhancing activity on ICs clearance is strengthened by both Angelicae Radix and Atractylodis Lanceae Rhizoma.

Experimental studies on immune-complex in situ type glomerulonephritis in rabbits treated with mai-luo-tong and natural indigo.

By injection of C-BSA, immune-complex in situ type glomerulonephritis was duplicated in rabbits and treated with Mai-Luo-Tong and natural Indigo. The results showed that proteinuria in the treated groups M and Q was decreased. The difference between group M and control group is statistically significant (P < 0.05). Under light and electron microscope, although glomerular basement membrane was irregularly thickened and subepithelial dense electron deposited in the treated group, but microthrombus, erythrocytes and platelets aggregation and leukocytes impaction were not seen within glomerular capillaries. Also in groups C, Q, M, mesenteric cell count was 99.40 +/- 18.53, 92.87 +/- 17.89, 66.55 +/- 7.75 respectively, the M. Q groups are compared with group C, the result is of statistical significance (P < 0.05) and there is no apparent glomerular fibrosis in the treated groups.

Immune functional impairment in patients with clinical abnormalities and silicone breast implants.

Silicone, previously thought to be a biologically inert and harmless material, has now been reported to elicit antibody response and to be responsible for adjuvant disease in humans. The present study was designed to evaluate the immune function of forty individuals who had undergone silicone breast augmentation for a period of longer than ten years and who were compared with 40 sex and age-matched controls. The following immunological functions were studied: lymphocyte subset analysis, lymphocyte mitogenic response, NK cytotoxic activity and markers for autoimmunity such as ANA, rheumatoid factor immune complexes such as smooth muscle, myelin, and thyroid, and tissue antibodies. Results of lymphocyte subpopulation analysis showed significantly elevated T helper/suppressor ratio in 60% and significantly decreased T helper/suppressor ratio in 7.5% of the silicone implant group, while the control group showed increased helper/suppressor ratio only in 10% of tested individuals and no significant decrease in the T helper/suppressor ratio. There was 20% inhibition in T cell mitogenic responses in the silicone implant group, which is significant when compared to the controls. When NK cytotoxic activity was compared between the two groups, significant inhibition in the ability of lymphocytes to kill tumor target cells was observed in the silicone implant group. This inability of target cell lysis was attributed to the demonstrated lack of granularity of NK cells from the silicone implant group. There was significant increase in: immune complexes, anti-nuclear antibodies, anti-thyroid antibodies, anti-striated muscle cell antibody, and anti-myelin basic protein antibodies. These immunological abnormalities in individuals who underwent silicone breast augmentation indicate a mechanism of tissue injury to these patients, causing autoimmune diseases or syndromes. Since autoimmunity in some other conditions is associated with abnormalities in the HLA serotyping system, and since some collagen vascular diseases have been associated with a higher incidence of the HLA serotyping system, it is recommended that HLA studies be included in future investigations of immune-mediated abnormalities associated with silicone breast augmentation. Our findings here show definite abnormalities of the T helper/suppressor ratio, increased autoimmunity, as well as increased production of immune complexes. Silicone implants have been used in cosmetic and reconstructive surgery more than 30 years (Brown et al., 1960). The gel used in the implant is produced from silicone, which is then related with methyl chloride and polymerized to form stable polydimethylsiloxane (Brown, et al., 1960). There have been a number of reports describing the occurrence of connective tissue disease in patients after the implantation of silicone.(ABSTRACT TRUNCATED AT 400 WORDS)