Differential regulation of human blood monocyte and alveolar macrophage inflammatory cytokine production by nitric oxide.

BACKGROUND: Nitric oxide (NO) has been associated with airway inflammation in asthma. Our previous work suggests that NO functions in an anti-inflammatory capacity through downregulation of stimulated cytokine secretion by normal human alveolar macrophages. Functional differences between alveolar macrophages and blood monocytes are thought to be related to maturation. OBJECTIVE: The purpose of this study was to determine the effect of NO on stimulated cytokine production by monocytes from asthmatics and normal healthy controls. METHODS: Monocytes and alveolar macrophages were obtained from normal volunteers (n = 13) and asthmatics with atopy (n = 7). Monocyte and alveolar macrophage cultures were stimulated with 0.5 microgram/mL lipopolysaccharide +/- 1.0 mM DETA NONOate (releases NO in culture with t1/2 = 20 hours at 37 degrees C) and incubated for 24 hours. Cell-free supernatants were collected and assayed by ELISA for tumor necrosis factor-alpha (TNF) and granulocyte macrophage colony stimulating factor (GM-CSF). RESULTS: Nitric oxide did not inhibit TNF production in monocytes of asthmatics and normals (mean +/- SEM % TNF stimulation = 19.6 +/- 9.7). Similar to previous results, NO did inhibit alveolar macrophages (% TNF suppression = 60.6 +/- 4.4). To determine whether this differential effect of NO on the two cell populations was related to maturation, monocytes were matured by culture for 7 days. The in vitro matured monocytes demonstrated 51.7 +/- 7.9% suppression of TNF. For each cell population, the responses of the asthmatics and healthy controls were not different. The differential effect is not cytokine specific since similar results were obtained with GM-CSF. CONCLUSION: These results demonstrate a differential effect of NO on monocyte and alveolar macrophages cytokine regulation and this effect may be related to the state of maturation.

Managing latex allergy in patients and health care workers.

The new and important problem of latex allergy deserves the attention of all health care professionals and institutions. Latex products we use every day may cause serious consequences for patients and coworkers. All providers must develop a plan for protecting allergic patients and staff from latex exposure, and for managing allergic reactions should they occur.

Shared IgE-binding sites among separated components of natural rubber latex.

BACKGROUND: IgE-mediated allergy to proteins present in natural rubber latex is a well-recognized problem. Latex contains a complex mixture of proteins ranging in molecular weight from 6 to > 200 kD. OBJECTIVE: The aim of this study was to determine whether shared allergenic sites exist on separate latex components. METHODS: Following electrophoresis, latex components at 14, 24, and 46 kD were electroeluted from SDS-polyacrylamide gels and used in ELISA inhibition and immunoblot inhibition studies of human latex-specific IgE antibodies. RESULTS: A minimum of 4 major allergenic sites (for convenience labeled A through D) were found to exist in 3 components of nonammoniated latex. Minimally, 2 are present in the 14-kD component (A, B) and 3 in the 24-kD component (A-C). The 46-kD fraction has 3 or more antigenic sites (A, C, D) but lacks one (B) that is present in both the 14- and 24-kD components. CONCLUSIONS: Four different IgE-binding moieties were detected among three latex protein components (14, 24 and 46 kD). Some of these allergenic sites were shared by two or more components. Recovery of these and others from fragmented latex components will allow identification of their amino acid composition and their availability will ultimately lead to better diagnostic and therapeutic options for patients with latex allergy.

Latex hypersensitivity in emergency medical service providers.

BACKGROUND: Emergency medical service providers have a high degree of exposure to latex products. Patients utilizing emergency medical services can be allergic to latex products used during rescue efforts. OBJECTIVE: To determine the prevalence of latex hypersensitivity among emergency medical service providers. METHODS: Study questionnaires were distributed to a group of emergency medical service providers. Skin prick testing was performed using latex, common aeroallergens, and food extracts. Patch testing was done using latex and individual rubber additives. Serum latex-specific IgE was also measured. RESULTS: A total of 93 completed surveys were collected. Average exposure to latex in the work environment was 8.2 years. Eighty-four (90%) used latex gloves routinely at work. Of those, thirteen (14%) gave history of reaction to latex gloves. Sixty-two percent were not aware of the possibility of latex allergy in themselves or their patients. Forty-one (44%) had skin testing. Of those, four (10%) had positive prick tests for at least one of the four latex preparations used. Five had positive skin tests to avocado extract without supporting clinical history. Two had positive skin tests to banana, one with supporting clinical history for banana allergy. No food cross-reactivity with latex was demonstrated. Latex-specific serum correlated with prick skin test results. No positive reactions were noted with patch testing. CONCLUSIONS: A significant percentage of emergency medical service providers were not aware of the occupational risk of latex allergy or the potential risk in their patients. A positive prick skin test for latex was present in 4 of 41 (10%), representing one-third of those who reported symptoms from latex exposure.

A guinea pig model of hypersensitivity to allergenic fractions of natural rubber latex.

Allergy to natural rubber latex is a growing medical problem with life-threatening aspects. The aim of this study was to learn if guinea pigs could serve as a suitable model for immediate-type hypersensitivity to latex. Guinea pigs were immunized either with whole non-ammoniated latex extract, or with one of nine SDS-PAGE-separated components. Other animals were injected with electroeluted latex components localized on gel at 14, 24 and a cluster around 45 kD. Before and after immunization, sera from the animals were examined by ELISA, immunoblots, passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis. Latex-specific antibodies were detected by ELISA and immunoblots in sera from all immunized animals. PCA assays showed that the guinea pigs had homocytotropic antibodies dilutable to 1:250. PCA was abolished when sera from animals immunized with allergens in alum were heated at 56 degrees C for 30 min indicating the antibodies were of the E isotype. Passive systemic anaphylaxis was induced in 4 of 10 guinea pigs. The results show that guinea pigs are capable of making antibodies to latex protein components that mediate dermal and systemic anaphylaxis, paralleling the spectrum of clinical and laboratory findings of humans with immediate-type clinical latex hypersensitivity.

Latex hypersensitivity: its prevalence among dental professionals.

Reports of hypersensitivity to latex are growing among oral health care workers, who have a high degree of exposure to latex products. The authors undertook a study to determine the prevalence of latex hypersensitivity among oral health care workers in a hospital dental practice. Among the 34 people who participated in the study, 12 percent had positive results in a skin prick test for latex. This suggests that the true prevalence rate of immediate hypersensitivity to latex in this group of oral health care workers is similar to that in other health care workers who use latex gloves frequently.

Latex hypersensitivity: a case study.

We report 16 cases of latex allergy and the diagnostic methods used to determine sensitivity. By history, eight had usually experienced anaphylaxis during operative procedures, and eight experienced contact urticaria. Skin prick tests were positive in all subjects and negative in ten controls. In vitro analysis by ELISA for latex-specific IgE was positive in only three subjects. No adverse reactions occurred during testing. We conclude that prick skin testing is the preferred diagnostic method, and that the in vitro method used in this study has an unacceptable lack of sensitivity.

Indirect immunofluorescence on rat bladder transitional epithelium: a test with high specificity for paraneoplastic pemphigus.

BACKGROUND: Paraneoplastic pemphigus is a blistering disease with specific serum immunoprecipitation findings. Although immunoprecipitation studies allow accurate diagnosis, they are time-consuming, expensive, and not readily available. In contrast, indirect immunofluorescence (IIF) testing of serum on transitional rat bladder epithelium is a simple and inexpensive method available to any immunopathology laboratory. OBJECTIVE: Our purpose was to determine the specificity of positive IIF on rat bladder epithelium for paraneoplastic pemphigus. METHODS: The IIF findings in four index cases of paraneoplastic pemphigus were compared with the findings in 47 patients with a variety of malignant neoplasms and no associated blistering disease as well as 49 patients with vesiculobullous or lichenoid disease but no neoplasia. RESULTS: IIF was negative in all patients with neoplasia and no blistering disease and negative in all but one of the patients with vesiculobullous or lichenoid disease without neoplasia (98.9% specificity). CONCLUSION: IIF on transitional rat bladder epithelium appears to be a highly specific test for paraneoplastic pemphigus. Because of its simplicity and inexpensiveness, we suggest that IIF be performed on transitional epithelium in any suspected case of paraneoplastic pemphigus.

Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase.

We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol. The modified enzyme was rapidly absorbed after intramuscular injection and had a half-life in plasma of 48 to 72 hours. Weekly doses of approximately 15 U per kilogram of body weight maintained plasma adenosine deaminase activity at two to three times the level of erythrocyte adenosine deaminase activity in normal subjects. The principal biochemical consequences of adenosine deaminase deficiency were almost completely reversed. In erythrocytes, adenosine nucleotides increased and deoxyadenosine nucleotides decreased to less than 0.5 percent of total adenine nucleotides. The activity of S-adenosylhomocysteine hydrolase, which is inactivated by deoxyadenosine, increased to normal in red cells and nucleated marrow cells. Neither toxic effects nor hypersensitivity reactions were observed. In vitro tests of the cellular immune function of each patient showed marked improvement, along with an increase in circulating T lymphocytes. Clinical improvement was indicated by absence of infection and resumption of weight gain. We conclude that from the standpoints of efficacy, convenience, and safety, polyethylene glycol-modified adenosine deaminase is preferable to red-cell transfusion as a treatment for adenosine deaminase deficiency. Patients with other inherited metabolic diseases in which accumulated metabolites equilibrate with plasma could benefit from treatment with the appropriate polyethylene glycol-modified enzyme.