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PubMed1976

Delayed hypersensitivity skin testing for assessing anergy in the mid-south.

Although skin testing with ubiquitous antigens is widely employed to assess delayed hypersensitivity, little is known about the effect of geographic location on the frequency of skin test reactions to given antigens. To assess skin test reactivity in the mid-South, 82 hospitalized patients and 68 normal controls had skin tests with six antigens: histoplasmin, mumps, tuberculin purified protein derivative (PPD), Candida, Trichophyton, and streptokinase-streptodornase. Ninety-five percent of normal and 79% of hospitalized subjects without immunologically related disease reacted to at least one of the antigens. A high rate of anergy was found in a clinical setting of debilitation and malnutrition. If subjects in poor condition also were excluded, 93% of hospitalized patients reacted to at least one antigen. Rates of reactivity increased with higher concentrations of antigen. To assess anergy in the mid-South, it is recommended that patients be skin tested initially with histoplasmin, mumps, and PPD antigens. If the patient does not react to any of these, streptokinase-streptodornase and Candida albicans (Dermatophytin "O") should be applied.

Antigens↗

PubMed1983

Evidence of mitogenic activity in periodontitis-associated bacteria.

This study examines several periodontitis-associated bacterial isolates for the presence of mitogenic activity, as indicated by their capacity to stimulate unsensitized lymphocytes to undergo blastogenesis. Germfree mouse spleen cells responded vigorously to all of the bacterial sonic extracts tested. The kinetics and dose responses to these activators in germfree mouse spleen cell cultures paralleled those seen with the standard murine B-cell mitogen, Escherichia coli lipopolysaccharide. In contrast, Streptokinase-Streptodornase (Varidase; Lederle Laboratories) antigen elicited no response. Human cord blood lymphocytes also responded upon stimulation with these same bacterial isolates but failed to respond to Streptokinase-Streptodornase. The frequency, magnitude, and kinetics of these cord blood lymphocyte responses were remarkably similar to those seen with adult peripheral blood lymphocytes. However, in this and previous studies, individuals with unresponsive peripheral blood lymphocytes have been observed. Studies were initiated to determine whether these unresponsive leukocyte preparations truly lacked the capacity to respond to these bacteria or whether unresponsiveness reflected the presence of a regulatory cell population in these cultures. After the removal of the adherent cells from unresponsive peripheral blood lymphocyte cultures, the nonadherent cells were found to be responsive. Therefore, peripheral blood lymphocyte responsiveness appears to be regulated via an adherent cell population. The removal of adherent cells from unresponsive cord blood lymphocyte preparations resulted in a less consistent alteration to responsiveness. However, cord blood lymphocyte preparations unresponsive at a standard cell density were shown to be responsive at altered cell densities.

Animals↗

PubMed2005

Alpha-melanocyte-stimulating hormone suppresses antigen-induced lymphocyte proliferation in humans independently of melanocortin 1 receptor gene status.

Studies in mice indicate that alpha-melanocyte-stimulating hormone (alphaMSH) is immunosuppressive, but it is not known whether alphaMSH suppresses human immune responses to exogenous Ags. Human PBMCs, including monocytes, express the melanocortin 1 receptor (MC1R), and it is thought that the ability of alphaMSH to alter monocyte-costimulatory molecule expression and IL-10 release is mediated by this receptor. However, the MC1R gene is polymorphic, and certain MC1R variants compromise receptor signaling via cAMP, resulting in red hair and fair skin. Here, we have investigated whether alphaMSH can suppress Ag-induced lymphocyte proliferation in humans and whether these effects are dependent on MC1R genotype. alphaMSH suppressed streptokinase-streptodornase-induced lymphocyte proliferation, with maximal inhibition at 10(-13)-10(-11) M alphaMSH. Anti-IL-10 Abs failed to prevent suppression by alphaMSH, indicating that it was not due to MC1R-mediated IL-10 release by monocytes. Despite variability in the degree of suppression between subjects, similar degrees of alphaMSH-induced immunosuppression were seen in individuals with wild-type, heterozygous variant, and homozygous/compound heterozygous variant MC1R alleles. RT-PCR of streptokinase-streptodornase-stimulated PBMCs for all five melanocortin receptors demonstrated MC1R expression by monocytes/macrophages, MC1R and MC3R expression by B lymphocytes, but no melanocortin receptor expression by T lymphocytes. In addition, alphaMSH did not significantly inhibit anti-CD3 Ab-induced lymphocyte proliferation, whereas alphaMSH and related analogs (SHU9119 and MTII) inhibited Ag-induced lymphocyte proliferation in monocyte-depleted and B lymphocyte-depleted assays. These findings demonstrate that alphaMSH, acting probably via MC1R on monocytes and B lymphocytes, and possibly also via MC3R on B lymphocytes, has immunosuppressive effects in humans but that suppression of Ag-induced lymphocyte proliferation by alphaMSH is independent of MC1R gene status.

Animals↗

PubMed1976

Treatment of horses with chronic diarrhea: immunologic status.

All chronically diarrheal horses given (orally) 2 series of treatments with normal horse serum recovered in 2 to 4 weeks. However, mild diarrhea sometimes persisted several months in the group of horses with severe diarrhea. Weight gains were approximately 35% in horses with severe diarrhea and approximately 10% in horses with mild diarrhea. Serum specimens from 12 diarrheal and 20 normal horses were examined for immunoglobulins by single radial immunodiffusion technique. Concentration of immunoglobulin A in serum of diarrheal horses was approximately 50% lower than that in serum of normal horses. By contrast, there was more immunoglobulin G in serum of diarrheal horses than in serum of normal horses. Phytohemagglutinin (PHA-M) responsiveness of blood lymphocytes showed transient suppression during the stage of severe diarrhea. The regaining of PHA-M responsiveness of lymphocytes was observed simultaneously with the recovery process. However, the responsiveness of lymphocytes in recovered horses remained markedly lower than that in normal horses. Allergic reactions in diarrheal and normal horses were studied by observing dermal response to injections of saline extracts from some of the horse feeds. A delayed hypersensitivity reaction to streptokinase-streptodornase and PHA-M was also studied. Allergic reactions to these extracts were not induced in either diarrheal or normal horses; however, inflammatory response to the extracts was approximately 50% greater in normal than in diarrheal horses. Response to intradermal injection of either streptokinase-streptodornase or PHA-M was significantly greater in normal horses than in diarrheal horses.

Animals↗

PubMed1977

Cellular immunity in adult marasmus.

Twelve patients with recent weight loss to less than 85% of standard weight-height ratio and a serum albumin level of at least 3 gm/100 ml were considered to have the adult equivalent to marasmus. Cellular immune function was assessed by delayed hypersensitivity skin testing to Monilia and streptokinase-streptodornase, peripheral lymphocyte count, proportion of T and B cells, whole blood and isolated lymphocyte transformation to phytohemagglutinin, pokeweed mitogen, concanavalin A, Monilia, and streptokinase-streptodornase. Significant impairment of skin test reactivity while in vitro responsiveness remained intact was noted in the marasmic patients. No impairment was found in 12 individuals with recent weight loss who remained at a weight greater than the 85% weight-height ratio. In four marasmic individuals in whom weight loss was arrested by nutritional repletion, skin reactivity returned without substantial change in weight. In this type of marasmus, both depleted nutritional status and weight loss must be present for impairement of skin test responsiveness. These findings confirm relative sparing of more vital functions dependent on protein metabolism in adult marasmus compared to the kwashiorkor-like syndromes of hypoalbuminemic malnutrition seen in adults.

Adult↗

PubMed1961

Failure of proteolytic enzymes to suppress post-traumatic inflammation. Double-blind control comparison on identical twins, after dermal abrasion.

Controlled reports on the successful use of proteolytic enzymes to suppress post-traumatic inflammatory response have been based on animal subjects that were given the drug before inflammation was provoked and in the equivalent of 10 to 1,000 times maximum human dosage. All previous favorable reports on human subjects were based on uncontrolled experiments. In the present study, the first controlled human experiment, identical twins were identically treated with dermal abrasion of the face, to remove deep acne scarring. Using double-blind technique, one of them received "inert" parenteral and buccal vitamin medication. The other received maximum recommended therapeutic dosage of three proteolytic enzymes-streptokinase and streptodornase buccal tablets, and intramuscular trypsin. No differences in edema, inflammatory response, pain or speed of healing were noted.

Cicatrix↗

PubMed1975

Delayed cutaneous hypersensitivity and peripheral lymphocyte counts in patients with advanced cancer.

One hundred eighty-three patients with advanced solid neoplasms were tested for their ability to react to four common skin test antigens (tuberculin PPD, streptokinase-streptodornase, mumps, and Monilia) and their ability to develop delayed cutaneous hypersensitivity (DCH) to 2, 4 dinitrochlorobenzene (DNCB). All patients were followed for at least 6 months or until death. Histologic tumor types studied were: melanoma (65), sarcoma (28), squamous cell carcinoma (23), and adenocarcinoma (67). The rate of progression of disease within 6 months of testing was lower in patients who had a positive response to a challenging dose of 50 mug of DNCB. Reactivity to recall antigens had no prognostic value except in patients with adenocarcinomas. Among patients with adenocarcinoma, those who reacted strongly to DNCB and one or more skin test antigens had the best prognosis, while those who were nonreactive to all had the worst prognosis (progression rate: 18% vs. 78%). Peripheral lymphocyte counts were related to the results of DCH to DNCB and skin tests. The preseence or absence of lymphocytopenia (count less than 1000/mm3) had prognostic value in patients who had positive skin test(s). In such patients, the disease progression rate was much higher in patients who were anergic to DNCB and who were lymphocytopenic (90% vs. 40%). These data suggest that DCH to DNCB, recall antigens, and peripheral lymphocyte counts are useful immunologic measurements in patients with advanced cancer. Although the prognostic value of each individual test is relatively limited, the predictive worth can be increased when multiple tests are employed. Pertinent findings reported in the literature are reviewed.

Adenocarcinoma↗

PubMed1989

[Postoperative, intra-abdominal adhesions--a new standardized and objective animal model and testing of substances for the prevention of adhesions].

80 male Sprague Dawley rats were divided in 8 groups of equal size. After median laparotomy defined abrasions of the serosa of abdominal wall, cecum and ileum were performed (400p, abrasive paper 280 grains/cm2, 8 cm2). The control group (I) received no medication. In the treatment groups 5 ml of the following agents were instilled before closure of the abdominal wall: normal saline (II), 16,250 IE Neomycin with 1250 IE Bacitracin (III), 30% dextrose (MW 70,000) (IV), 50,000 IE Streptokinase with 12,500 IE Streptodornase (V), or TCDO in concentrations of 10% (VI), 50% (VII), and 100% (VIII). All animals were relaparotomized on the 7th postoperative day, the adhesions were dissected and their extent was calculated by computer aid. Furthermore specimens were obtained for microscopic studies. Compared to the controls no reduction of adhesions could be achieved by dextrose. Significantly more adhesions were observed after treatment with Neomycin/Bacitracin. A reduction of about 23% was registered with normal saline and TCDO 10%. The greatest reduction of adhesions was seen after application of Streptokinase/Streptodornase as well as TCDO in concentrations of 50% and 100% (63%). The results were significant after evaluation with the t-test. Histologically there was a correlation between the extent of adhesions and the fibrin film. The new animal model has proven to result in reproducible data if used to evaluate substances for prevention of adhesions. Clinical studies with the best of these agents could serve as an approach to solve the problem of adhesion ileus.

Abdomen↗

PubMed1985

[Initial clinical results of the prevention of intraoperative adhesions in children].

Postoperatively in 2 to 6% of all cases the result was an intestinal obstruction caused by adhesion. The usual measures were without permanent success. Intraoperatively we applied in 20 children streptokinase-streptodornase in the abdomen. During relaparotomy we saw no adhesions in 40% of these cases, whereas in a control group in all cases adhesions were found.

Abdomen↗

PubMed1975

Abnormalities in cell-mediated immunity in patients with Cryptococcus neoformans infection.

Cryptococcin, streptokinase-streptodornase (SK-SD), mumps, and purified protein derivative (PPD) were used for skin testing and, with whole killed Cryptococcus neoformans, were used in migration inhibition and lymphocyte transformation assays of control subjects and patients with past or present disseminated C. neoformans infection. Cryptococcin was found to differentiate control subjects grouped by known Cryptococcus exposure. Cryptococcin and C. neoformans were effective in stimulating leukocyte migration inhibition and lymphocyte transformation in the cryptococcin skin test-positive control subjects. Fifteen apparently normal patients who had been cured of cryptococcosis were found, as a group, to have impaired responsiveness to skin testing with cryptococcin and mumps, minimal leukocyte migration inhibition when stimulated with cryptococcin or C. neoformans, but normal group responses to cryptococcin in Cryptococcus-induced lymphocyte transformation. Six patients with known predisposing conditions to disseminated infection (sarcoid, lymphoma, leukemia, steroid therapy) had markedly diminished responses to most skin tests and in vitro assays. It is suggested that the apparently normal individual who develops disseminated cryptococcal infection has subtle defects in cellular immunity that may have antedated and predisposed to infection.

Antigens, Fungal↗

PubMed1975

Alteration of T cell function in healthy persons with a history of thymic x-irradiation.

The possible late effects of x-irradiation to the infantile thymus were investigated by studying immune functions in 12 healthy persons with a history of thymic x-irradiation and healthy control subjects. No differences were found in serum immunoglobulin values, humoral antibody levels, lymphocyte counts, and lymphocyte reactivity to phytochemagglutinin, vaccinia virus, purified protein derivative (PPD), and allogeneic cells. The irradiation group exhibited cellular hyperresponsiveness to streptoskinase-streptodornase (SK-SD). In contrast, mean skin and in vitro lymphocyte responses to Candida albicans were depressed in the patients with thymic irradiation. A dissociation of these two Candida responses was found in only 1 of 14 healthy control subjects but in 7 of 12 irradiated individuals. While thymic irradiation did not result in impaired immunologic defenses leading to clinical disease, it caused alterations in T cell responses similar to those reported in patients with chronic mucocutaneous candidiasis.

Adolescent↗

PubMed1975

Depression of cell-mediated immunity in atopic eczema.

Prompted by recent observations that the thymus exerts an important regulatory influence over IgE antibody production in lower species, we conducted studies of immune function in 21 patients with atopic eczema to seek evidence for a similar relation in man. Skin tests for delayed hypersensitivity to Candida albicans and streptokinase-streptodornase (SK-SD) revealed a striking degree of anergy that correlated with the severity of the eczema. A correlation was also noted between the extent of the dermatitis and the magnitude of the serum IgE concentration. Other immunologic abnormalities did not appear related to the severity of eczema put pertained to the group as a whole. These included significantly (p = less than 0.0001) lower mean percentages of spontaneous sheep erythrocyte (E) or T cell rosettes and of rosettes with neuraminidase-treated sheep erythrocyte (En) rosettes, and significantly lower in vitro lymphocyte responsiveness of the mitogens concanavalin A (p = 0.0013) and poleweek mitogen (p = 0.0002) and to Candida antigen (p = 0.0017) than in normal subjects. Responses to phytohemagglutinin and tetanus toxoid were also depressed but differences were not statistically significant. An increased percentage (p = 0.0324) of peripheral blood B lymphocytes bearing the complement receptor was noted, but, except for a slight increase in lymphocytes bearing IgD, percentages of lymphocytes bearing other immunoglobulins (including IgE) were not elevated.

Adolescent↗

PubMed1975

The effect of aging and acute illness on delayed hypersensitivity.

A group of standard antigens (monilia, mosquito, mumps, purified protein derivative [PPD], staphylococcus toxoid, streptokinase-streptodornase [sk-sd] and trichophyton) were applied to 321 normal volunteers, 60 patients admitted to a medical ward, and 41 patients in an intensive care unit (ICU) to evaluate their delayed hypersensitivity skin test response. Eighty-eight per cent of the normal subjects reacted with at least 5 mm. induration to one or more skin tests without any decrease in reactivity occurring with increasing age. In the hospitalized group, only 62 per cent of the ward and 63 per cent of the ICU patients reacted to the same skin tests. All (8/8) anergic ICU patients tested after discharge regained normal reactivity. Acute illness but not increasing age will impair the delayed hypersensitivity skin test response.

Acute Disease↗

PubMed1980

In vivo and in vitro cell-mediated immunity to tetanus toxoid in adults.

The purpose of this study was to evaluate tetanus toxoid (TT) as an indicator of cutaneous delayed hypersensitivity (CDH) in adults. Fifty-two normal subjects, aged 25 to 64 yr, were skin tested with TT and streptokinase-streptodornase (SK/SD). Lymphocyte transformation was studied in seven normal TT reactors, four normal TT nonreactors, and seven hospitalized anergic patients. CDH was common with both TT and SK/SD; 90% of the adults, aged 25 to 39 yr, had CDH reactions to TT and 79% had CDH reactions to SK/SD. In adults aged 40 to 64 yr, 75% had DCH reactions to TT and 59% had CDH reactions to SK/SD. Lymphocyte transformation to TT correlated well with TT skin-test results. Punch biopsy specimens of TT reactions 48 hr after skin testing demonstrated DCH. We conclude that TT is an excellent antigen for assessing the presence or absence of CDH in adults aged 25 to 64 yr.

Adult↗

PubMed1981

Role of cell-mediated immunity in Hymenoptera allergy.

Currently there is little information regarding the immunologic mechanisms responsible for large local reaction (LLR) after Hymenoptera stings. To investigate this question, we measured in vitro lymphocyte proliferation and delayed skin reactivity to venom antigens in 10 subjects with LLR (six with LLR only and four with LLR and systemic reactions), seven subjects with systemic reactions, and eight nonallergic controls. The lymphocyte response to venoms in the LLR group was greater than that in either the systemic reactor group (p less than 0.05) or the control group (p less than 0.001). In contrast, lymphoproliferative responses to Candida albicans, streptokinase-streptodornase, and phytohemagglutinin were comparable in the three groups. Forty percent of the LLR group had positive delayed skin tests to venom antigens, and none of the patients in the systemic reactor group had such responses. These findings suggest that cellular immune mechanisms play a role in the pathogenesis of LLR after Hymenoptera stings.

Candida albicans↗

PubMed1982

Collagens act as ligands to stimulate human monocytes to produce mononuclear cell factor (MCF) and prostaglandins (PGE2).

Blood mononuclear cells from patients with rheumatoid arthritis produce the lymphokine, leukocyte inhibitory factor (LIF) in response to collagens in vitro, and blood monocytes release prostaglandins (PGE2) and a factor, mononuclear cell factor (MCF) which stimulates collagenase and PGE2 production by cultured synovial cells. We therefore examined the effect of collagens on the production of PGE2 and MCF. Blood mononuclear cells from 6 patients with rheumatoid arthritis and 6 normal subjects were cultured in native human types I, II, or III collagen-coated tubes, or with streptokinase-streptodornase (SK-SD), and the supernatant media derived from these cultures analyzed for the presence of MCF, PGE2, and LIF. Types II and III collagens, as well as SK-SD, markedly stimulated MCF production by the cells from all 12 subjects (MCF activity, expressed as a mean stimulation index (SI) +/- SEM, was 43 +/- 12 for type II, 33 +/- 7 for type III, and 37 +/- 23 for SK-SD). Type I collagen was less stimulatory (mean SI 10 +/- 7). Cells from the patients with rheumatoid arthritis, but not the normal subjects, produced LIF in response to types II or III collagens but not to type I collagen. PGE2 production by blood mononuclear cells paralleled that of MCF, although abrogation of PGE2 release with indomethacin did not reduce MCF production. alpha chains purified from denatured collagens also stimulated MCF production. Using cells from patients with rheumatoid arthritis, type II collagen stimulated production of all three factors in the presence of polymyxin B or fibronectin-depleted serum, suggesting, respectively, that neither endotoxin nor fibronectin were responsible for their generation. Monocytes, purified from normal blood by an adherence technique, but not lymphocytes depleted of monocytes, released MCF and PGE2 when cultured with type II collagen. These results demonstrate that collagens can act as ligands to stimulate monocytes, as well as antigens to stimulate sensitized lymphocytes, to produce soluble factors that may contribute to the destruction of connective tissue.

Arthritis, Rheumatoid↗

PubMed1982

Instillation of fibrinolytic enzymes in the treatment of pleural empyema.

Acute pleural empyema which is not amenable to pleural puncture or closed thoracic drainage should be treated operatively by decortication or, in persistent cavities, by open thoracostomy drainage. In the last 2 years we have instilled 500,000 IU of fibrinolysines (streptokinase and streptodornase) per day into the pleural cavity of 27 patients with pleural infections requiring closed intrapleural drainage. By means of this treatment, pus and fibrinous membranes are liquefied and necrotic tissue is discharge. Therapeutic success is indicated by considerably increased fluid drainage about one hour after instillation. This therapy was performed for an average of 5 days. In 12 patients (44%) pleural empyema could be cured. In the other 15 cases decortication, and in 3 of them open thoracostomy drainage, was necessary. In our opinion intrapleural instillation of fibrinolytic enzymes should be added to the well-recognized method of treatment of pleural empyema, although not replace them.

Acute Disease↗

PubMed1982

Immunologic evaluation of patients with polychlorinated biphenyl poisoning: evaluation of delayed-type skin hypersensitive response and its relation to clinical studies.

Polychlorinated biphenyl (PCB) poisoning causes many physiological abnormalities including immune suppression. Cellular immunity was studied in 30 PCB-poisoned patients and 50 normal human subjects. PCB poisoning caused suppression of cellular immunity such as the delayed-type skin response to streptokinase and streptodornase. The suppression of cellular immunity was correlated with the severity of the disease. Thus evaluation of the immune function may be helpful for the diagnosis of PCB poisoning.

Adolescent↗