Immunomodulatory effect of endotoxin on the development of latex allergy.

Background: Although numerous studies have been conducted delineating the clinical manifestations of latex allergy and characterizing the protein allergens, little is known regarding the natural history of the disease.

Objective: These studies were undertaken to investigate the immunomodulatory role of inhaled endotoxin on the development of latex-specific IgE-mediated responses to natural rubber latex (NRL) proteins by using a mouse model.

Methods: Female BALB/c mice were exposed to 25 microg of NRL proteins with or without increasing concentrations of endotoxin (50-25,000 EU) through the respiratory tract.

Immunotoxicity of medical devices. Symposium overview.

Determination of the ability of a medical device to interact with the immune system currently involves assessment of the immunogenic potential and biocompatibility of the device or an extract of the device. However, implants are often in the body for extended periods of time and/or are placed by a surgical procedure that in and of itself will generate an acute inflammatory response. This symposium discussed studies that have been performed to evaluate the immunogenicity of various devices consisting of several different compositions (i.

Characterization of the allergen(s) in latex protein extracts.

Background: Immediate hypersensitivity to latex, induced by natural latex proteins remaining on the finished products, may lead to severe anaphylactic reactions.

Methods: We investigated the distribution of latex proteins by molecular weight and identified the specific allergenic molecules. Proteins extracted from various latex products were compared with those extracted from raw latex sap, both ammoniated and nonammoniated.

Cornstarch powder on latex products is an allergen carrier.

Allergic reactions of the upper respiratory tract during use of powdered latex rubber gloves have been recently associated with sensitivity to latex. We have studied the ability of cornstarch powder to bind latex proteins and evaluated allergenic properties of the bound protein. Allergenicity was determined by competitive inhibition of human anti-latex IgE binding to solid-phase latex antigen.

Latex-associated allergies and anaphylactic reactions.

The recent reports of severe anaphylactic reactions and several fatalities caused by contact with latex-containing products raised concerns in the medical community. Although hypersensitivity to natural rubber has been widely reported in the literature, the prevalence and severity of reactions have rapidly increased in the last few years. Latex proteins, constituents of natural latex, appear to be responsible for the sensitization.

Antitumor activity of phytic acid (inositol hexaphosphate) in murine transplanted and metastatic fibrosarcoma, a pilot study.

We have previously reported that phytic acid (inositol hexaphosphate or InsP6), a natural constituent of cereal diet, when administered in drinking water exerts a consistent antitumor effect on experimental colon cancer in vivo. The objective of this study was to determine whether InsP6 has similar anti-neoplastic effect on other tumor models, such as murine fibrosarcoma. We report that intraperitoneal injection of InsP6 reduces growth of subcutaneously transplanted fibrosarcoma (FSA-1) in mice, prolongs survival of tumor-bearing mice and reduces the number of pulmonary metastases.

Adjuvant immunotherapy in melanoma: a new approach.

Patients with metastatic cutaneous melanoma to two or more regional lymph nodes have an extremely poor prognosis despite radical lymphadenectomy. In an attempt to improve the survival and to determine the safety of a new method of tumor specific adjuvant immunotherapy in such a high risk group of patients, nine patients were studied. Three to four weeks after regional lymphadenectomy, each of them received a single intradermal injection of Bacillus Calmette-Guérin.

An immunological aspect of melanoma and its potential application in adjuvant therapy.

In an attempt to understand some of the natural immunological characteristics of cutaneous melanoma so that we can plan justifiable immunotherapeutic approaches, 23 patients were studied. The autologous leukocyte migration inhibition assay was utilized to assess in vitro their tumor-specific cellular immunity. This assay was specifically used because when presensitized lymphocytes are exposed to the same antigen, they release lymphokines which inhibit the natural migration of the leukocytes.

Inositol-phosphate-induced enhancement of natural killer cell activity correlates with tumor suppression.

In recent studies, we have demonstrated that inositol hexaphosphate (InsP6) inhibits experimental colon carcinogenesis. Since natural killer (NK) cells are involved in tumor cell destruction, we investigated the effect of InsP6 on murine NK cell activity. We show that; (i) 1,2-dimethylhydrazine (DMH), a colon carcinogen, depresses NK activity; (ii) in vivo treatment of mice with InsP6 enhances baseline NK activity and reverses DMH-induced depressed NK activity with an inverse correlation (r = -0.

Anti-tumor activity of recombinant tumor necrosis factor on mouse fibrosarcoma in vivo and in vitro.

The experiments presented were designed first to determine the effects of rTNF on the methylcholanthrene-induced fibrosarcoma (FSA-1) in C3H/JSed mice and second to determine whether the observed effects are the result of direct action by rTNF on the tumor or whether rTNF acts as a mediator of other effector mechanisms. Mice received syngeneic FSA-1 fibrosarcoma cells either s.c.

Thymic factor-induced reduction of pulmonary metastases in mice with FSA-1 fibrosarcoma.

The biological activities of two thymic factors, serum thymic factor thymulin normally present in serum and thymosin alpha-1 (Ta-1) extracted from the thymus gland, have been studied. The effects of the factors on the growth of pulmonary metastases and survival of mice were evaluated in pathogen-free C3H/fSed males. Mice were injected i.

Effects of radiation therapy on T-lymphocyte subpopulations in patients with head and neck cancer.

Cellular immunity was assessed in 85 patients with head and neck cancer with monoclonal antibodies to lymphocyte surface antigens that identify total T cells, helper cells, and suppressor cells. The control group consisted of 22 healthy volunteers. Nine patients who had surgical procedures for benign diseases were also studied.

Thymosin alpha 1-induced modulation of cellular responses and functional T-cell subsets in mice with experimental autoimmune thyroiditis.

The effects of Ta-1, a peptide constituent of thymosin fraction 5, were studied on murine autoimmune thyroiditis using two congenic strains of mice, B10.Br (Br) and B10.D2 (D2), which are sensitive and resistant to experimental autoimmune thyroiditis (EAT) induction, respectively.

Experimental autoimmune thyroiditis: modulation of the disease level in high and low responder mice by thymosin.

Experimental autoimmune thyroiditis (EAT) in mice is characterized by production of anti-thyroglobulin autoantibodies and lymphoid infiltration of the thyroid gland. The pathogenesis of EAT is genetically controlled, but its mechanism is not yet clear. To investigate the mode of the expression of genetic control in the development of the disease, we attempted to modulate immune responses with thymosin fraction 5 (T-5) in mice which are either high or low responders to thyroglobulin.

Adriamycin induced immunomodulation: dependence upon time of administration.

The immunomodulating capabilities of the anti-neoplastic agent, Adriamycin, were investigated. The day of Adriamycin administration to mice was varied from -15 to -1, day 0 being when mice were either immunized or sacrificed and their spleen cells sensitized in culture. Humoral and cellular immune responses against allogeneic or xenogeneic cellular antigens in mice and in culture, as well as phagocytic and ADCC activities were evaluated using spleen cell populations.

Augmentation of the development of immune responses of mice against allogeneic tumor cells after adriamycin treatment.

In C57BL/6J mice, depending on the dose of P815 cells used for immunization, Adriamycin exerted different effects on the cell-mediated lytic response and complement-dependent cytotoxicity. At the dose of 3 X 10(7) P815 cells, Adriamycin treatment had no apparent effect on cell-mediated lytic response regardless of timing of drug treatment. At lower doses of antigen (10(7) or 5 X 10(6) cells), the response was augmented in Adriamycin-pretreated mice.

Selective imbalances of cellular immune responses by adriamycin.

It has been demonstrated that spleen cells from mice treated with adriamycin not only develop an increased cell-mediated immune response during culture with allogeneic tumor cells, but also have increased phagocytic activity following culture, respond to heat-treated (45 degrees C) alloantigen, develop an increased suppressor cell function, and are less sensitive to a suppressor cell activity. Thus, changes in spleen cell subpopulations occurring in the donor mice consequent to drug treatment result in demonstrable selective imbalances of cellular functions involved in the immune response. One cell type which has been implicated as being necessary in the expression of all these functions is the monocyte-macrophage, and it is suggested that an effect of adriamycin on progenitors of this cell type may lead to the imbalances.

Autoimmune murine thyroiditis IX. Relationship of humoral and cellular immunity to thyroiditis in high and low responder mice.

Good responder (C57/Br/cd) and poor responder (C57BL/10) mice were immunized with mouse thyroid extract in Freund's complete adjuvant. The good responder mice first showed antibody to thyroglobulin on the seventh day while the poor responder animals had slightly lower titers and antibody did not appear until day 12. The first signs of thyroid infiltration appeared on day 4 in the responder strain, and severe lesions were seen between the third and fifth week.

The macrophage disappearance reaction (mdr) as an in vivo test of delayed hypersensitivity in mice.

The macrophage disappearance reaction (MDR), as an invivo analogue of in vitro tests for delayed hypersensitivity, was utilized in mice with M. tuberculosis or mouse thyroid extract (MTE). The optimal schedule for the induction of macrophages in peritoneal exudates and the optimal concentration of antigen for the MDR were determined.

Acute graft-versus-host reaction in mice. I. Cellular events.

Cellular events in the spleen during the development of acute GvH reaction in lethally irradiated recipients of allogeneic lymphocytes may be divided into 6 interrelated processes: (1) entering and lodging in the spleen of about 17% of inoculated cells which forms the compartment of potentially reactive cells; (2) transformation (recruitment) of about 30% of cells lodged in the spleen into large pyroninophilic cells (LPC), a process lasting about 12-16 hr; (3) proliferation of recruited LPC by five successive divisions with a Tc of about 12 hr; (4) transformation of LPC into non-LPC; (5) proliferation of non-LPC by one division, with a Tc of about 8 hr; and (6) migration of mature immunologically active cells from the spleen. The last process correlates well with the concomitant appearance of lymphocytes in the peripheral blood (killer cells) and with the time of acute death among inoculated mice.

Studies on the mechanism of specific immunological unresponsiveness. II. Immunological properties of lymphoid cells from normal, immunized and immunologically unresponsive mice transferred into lethally irradiated recipients.

The immunological capacity of lymphoid cells from mice rendered tolerant to high and low doses of BSA was investigated. The tolerance was induced by multiple injections of high and low doses of antigen through the period of 30 days. Lymph node and bone marrow cells from tolerant animals were transferred into lethally irradiated syngeneic recipients.

Acute graft-versus-host reaction in mice. 3. Organ distribution of injected 51 chromium labeled lymphocytes.

The distribution of labeled lymph node cells, causing an acute GvH reaction in lethally irradiated allogeneic recipients, was studied. Lymph node cells of C57BL mice were labeled with 51Cr and injected into lethally irradiated: a) C57BL mice, b) CBA mice, c) CBA mice sensitized to C57BL antigens prior to irradiation, d) CBA mice splenectomized before irradiation. Two more experimental situations were studied in which C57BL donors of lymph node cells were: e) presensitized to CBA antigens, or f) deprived of T-lymphocytes.

Autoimmune murine thyroiditis. VIII. Role of different thyroid antigens in the induction of experimental autoimmune thyroiditis.

Mice of the C57Br strain, which are susceptible to the induction of autoimmune thyroiditis with mouse thyroglobulin, and C57Bl mice, which are resistant, were immunized with human and rabbit thyroglobulins in Freund's complete adjuvant. Susceptible strain C57Br developed higher degrees of thyroid infiltration than the resistant strain. The results indicate that the responses to xenogeneic (foreign) thyroglobulins parallel allogeneic and syngeneic (mouse) thyroglobulin.