Formulation and Validation of Recombinant Antigens CFP10 and ESAT6 for Tuberculosis Diagnosis

Abstract The rapid and accurate diagnosis of tuberculosis (TB), especially considering limited resources, is still a challenge. Development of new methodologies and tests are needed to overcome several disadvantages of the available standard tests. We evaluated the diagnostic potential of two antigens specific for Mycobacterium tuberculosis, the CFP10 and ESAT6 recombinant proteins, and developed stable formulations thereof. Sensitivity and specificity of the delayed-type hypersensitivity (DTH) skin testing and the induction of gamma interferon production (IFN-γ) by lymphocytes, as a non-invasive test, were evaluated using the CFP10 and ESAT6 protein formulations. The recombinant proteins produced by our group presented a high DTH response and the ability to differentiate between tuberculosis infection, BCG vaccination, and the contact with non-tuberculous mycobacteria (NTM). The production of IFN-γ by stimulation with individual and combined proteins was detected in a panel of 40 individuals and showed a specificity of 100% and a sensitivity of 90% when the two proteins were used together. Lyophilized formulations were stable under all conditions, while soluble formulations were stable under freezing at -20 ºC and -80 ºC. The proposed formulations containing the ESAT6 and CFP10 recombinant antigens constitute satisfactory tools for TB testing, suitable to be developed and implemented in a large-scale trial.

Circulating levels of chemokines in patients with psoriasis vulgaris and their association with disease severity: A case–control study from North India

Background: Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and incomplete differentiation of epidermis, and accumulation of neutrophils and proinflammatory T cells in epidermis and dermis. Chemokines are believed to be the main players mediating the chemotaxis of leucocytes to the lesional site. Previous studies have established the role of various chemokine ligands and receptors at the lesional site in psoriasis. Aims: In this study, we have compared the serum levels of various chemokines, namely, inducible protein-10 (IP-10) (CXCL10), MCP-1 (CCL-2), monokine induced by gamma interferon (MIG) (CXCL-9), RANTES (CCL5), interleukin (IL)-8, and eotaxin in patients with chronic plaque psoriasis with that of healthy controls. We also studied whether the chemokine levels varied within different patient groups based on various clinical and demographic parameters, and if any of these chemokines correlated with disease activity. Methods: We studied 40 patients with chronic plaque psoriasis from a single center. Their clinical and demographic details were recorded in predesigned prforma. Patients with unstable forms of psoriasis like guttate, erythrodermic, or pustular psoriasis were excluded. The serum chemokine levels were measured by flow cytometry–based bead array set system. The serum levels of the patients were compared with that of 25 healthy controls. A subgroup analysis was also done to study the correlation of chemokine levels with age, sex, duration, and severity of disease. Results: We observed a significant decrease in serum level of all these chemokines in patients, when compared with that of healthy controls. We also found that MIG levels showed a positive correlation with disease severity based on Psoriasis Area and Severity Index. Limitations: The major limitation of the study is lack of data on the lesional chemokine levels compared to serum chemokines. Conclusion: The inflammatory process in psoriasis is orchestrated through chemokines. MIG is a potential serum biomarker for assessing disease severity.

Clinical significance of cytokine changes in acute and chronic brucellosis before and during treatment / 中华地方病学杂志

Objective To observe the levels of peripheral blood cytokines interferon-γ (IFN-γ)and interleukin-4 (IL-4) in patients with acute and chronic brucellosis before and during treatment,and to understand the differences of two immunocytokines in acute and chronic stage of brucellosis,and the effect of antibacterial therapy on these two cytokines to provide immunological basis for clinical evaluation of the therapeutic effect of brucellosis.Methods Research subjects were 36 pre-treatment acute brucellosis and 36 pre-treatment chronic brucellosis and 36 dur-treatment acute brucellosis and 36 dur-treatment chronic brucellosis,which were selected from Ulanqab Center for Endemic Disease Prevention and Control of Jining City with 25 local healthy persons as healthy controls.The levels of IFN-γ and IL-4 in serum were measured by enzyme-linked immunosorbent assay (ELISA) in patients with acute and chronic brucellosis and control group before and during treatment.Parameters of IFN-γ and IL-4 were analyzed with One-Way ANOVA analysis in pre-treatment and dur-treatment acute brucellosis,chronic brucellosis and control groups.Results The means of IFN-γ [(462.79 ± 47.94),(431.92 ± 40.39),(280.50 ± 40.48) ng/L] and IL-4 [(606.11 ± 51.86),(550.66 ± 51.56),(383.24 ± 53.98) ng/L] were significantly different in the three groups before treatment (F =141.84,139.28,P ＜ 0.05);Compared to control group,the levels of IFN-γ and IL-4 in acute brucellosis and chronic brucellosis were significantly increased before treatment (P ＜ 0.05).The levels of IFN-γand IL-4 in the acute brucellosis were significantly increased compared to those of chronic brucellosis before treatment (P ＜ 0.05).After about ten days antibiotic therapy,the means of IFN-γ [(356.05 ± 43.75),(368.61 ± 35.69),(280.50 ± 40.48) ng/L] and IL-4 [(487.31 ± 51.59),(496.73 ± 48.70),(383.24 ± 53.98) ng/L] were significantly different in the three groups (F =39.57,41.99,P ＜ 0.05).Compared to control group,the levels of IFN-γ and IL-4 in acute brucellosis and chronic brucellosis were significantly increased during treatment (P ＜ 0.05).The levels of IFN-γand IL-4 in the acute brucellosis were not significantly different compared to those of chronic brucellosis during treatment (P ＞ 0.05).Conclusion Different immunological characteristics of cytokines in peripheral blood of patients with acute and chronic brucellosis before treatment have affected the therapeutic effect and clinical outcomes.

High level IFN-γ may be one of the characteristics of chronic brucellosis / 中国人兽共患病学报

We sought to compare the level of peripheral blood gamma interferon(IFN-γ),interleukin 4 (IL-4),TGF-β1,IL-10 and IFN-γ/IL-4 between acute brucellosis and chronic brucellosis to look for biochemical markers for chronic brucellosis.A total of 42 acute brucellosis and 42 chronic brucellosis cases were selected randomly from the Endemic Disease Prevention and Control Center of Ulanqab City as the research subjects with 20 local healthy persons as healthy control.Comparisons of IFN-γ,IL-4,TGF-β1,IL-10 and IFN-7/IL-4 in the three groups were tested by One-Way ANOVA analysis.Parameters of IL-4,IFN-γ,TGF-β1,IL-10 and IFN-γ/IL-4 in peripheral blood were analyzed with T-test between acute brucellosis with chronic brucellosis.Results showed that the mean of IFN-,IL-4,TGF-β1 and IFN-γ/IL-4 was significant difference in the three groups(F =6.86,11.90,12.25,4.60,P＜0.01),but not of IL-10(F=2.72,P＞0.05).The mean of IFN-γ,IL-4 andIFN-7/IL-4 was significant difference between acute brucellosis with chronic group(t=-1.99,82,-3.3,P＜0.05),but not of TGF-β1 and IL-10(t=-1.90,-1.81,P＞0.05).Combined with TGF-β1 and IL-10 levels,high level IFN-γ may be regarded as one of the biochemical markers for chronic brucellosis.

Influence of Yanyankang Powder on Th1/Th2 in rats with experimental autoimmune uveitis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the influence of Yanyankang powder on Th1/Th2 in rats with experimental autoimmune uveitis (EAU).</p><p><b>METHODS</b>The EAU models were induced in Lewis rats by immunization with interphotoreceptor retinoid binding protein (IRBP) 1177-1191 in complete Freund's adjuvant. The rats were randomly divided into 3 groups: a model control group, a Yanyankang group, and a prednisone group, 9 rats in each group. The model control group was intervened with saline solution by gavage. The Yanyankang group was intervened with Yanyankang powder 4 g/(kg day) by gavage. The prednisone group were intervened with prednisone acetate tablets 5 mg/(kg d) by gavage. All groups were intervened after immunization once every 2 days for 18 days and monitored by slit-lamp biomicroscopy daily until day 18. The levels of gamma interferon (INF-γ) and interleukin-10 (IL-10) in the supernatants of T cells were determined by enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) technology was used for measuring Th1 and Th2 related cytokine mRNA expressions.</p><p><b>RESULTS</b>Slighter intraocular inflammation was found in the Yanyankang group and the prednisone group than the control group. The levels of the IFN-γ and IL-10 in the supernatants of the spleen lymph node cells were 382.33±6.30, 155.87±4.46 μg/L in the Yanyankang group and 270.93±7.76, 265.32±11.88 μg/L in the prednisone group. Both had significant differences compared with the control group (941.53±8.59, 20.67±4.65 μg/L; =0.01). The PCR results showed the same tendency.</p><p><b>CONCLUSION</b>Yanyankang powder showed favorable effects in the rats with EAU by influencing the function of Th1 and Th2 cells.</p>

Effect of interferon gamma on immune factor and CD69 , CD107 a in patients with delayed type hypersensitivity / 中国生化药物杂志

Objective To investigate effect of interferon gemma on immune factor and CD69, CD107a in patients with delayed type hypersensitivity by interferon gamma.Methods 76 cases with delayed type hypersensitivity were selected and divided into 2 groups.38 cases in control group were treated conventional therapy, 38 cases in experiment group were treated by interferon gamma.Peripheral blood CD69, CD107a, immune factor, T cell subsets and the treatment efficiency were compared after the treatment.Results Compared with the control group, the serum CD69 and CD107a levels were lower in the experimental group (P<0.05), serum IgG and IgA levels were higher, the serum IgE level was lower (P<0.05), and the CD3 +,CD4 +,CD4 +/CD8 +level was higher, serum CD8 + was lower (P<0.05) .The effective rate of the treatment group was significantly higher than that of the control group (P<0.05) .Conclusion Interferon gamma has good clinical effect in the patients with delayed type hypersensitivity, and can effectively reduce the levels of CD69 and CD107a in the peripheral blood, and regulate the immune function of the body.

Role of interleukin-6, gamma interferon and adenosine deaminase markers in management of pleural effusion patients / Papel de la interleucina-6, el interferón gamma, y la adenosina desaminasa como marcadores en el tratamiento de pacientes con derrame pleural

OBJECTIVE: Pleural effusion is a common diagnostic and clinical problem. Neoplasms and tuberculosis are the most frequent diagnostic causes of such effusions. Conventional laboratory methods for diagnosis of such effusion are inefficient because tubercle bacilli are rarely seen in direct examinations of pleural fluid. The present study evaluates interleukin-6 (IL-6), gamma interferon (IFN-γ) and adenosine deaminase (ADA) as diagnostic tools in pleural effusion. METHODS: Interleukin-6, IFN-γ and ADA were measured in pleural fluid from the patients, with exudative pleural effusion from tuberculous, malignant and postpneumonic origin and transudative pleural effusion ofsystemic origin in order to evaluate the diagnostic utility ofthese. RESULTS: The three markers were detectable in all effusions with significantly high levels in exudative as compared to transudative effusions. There was a statically significant difference noticed in tuberculous as compared to malignant andpostpneumonic origin and transudative pleural effusion. CONCLUSION: We concluded that IL-6, IFN-γ and ADA levels in pleural effusion are sensitive parameters to differentiate an exudate from a transudate and they can also differentiate exudates of different aetiology. Finally, the results suggest that there is a remarkable difference in production of these three markers in exudative pleural effusions as compared to transudative pleural effusions.

OBJETIVO: El derrame pleural es un problema diagnóstico y clínico común. Las neoplasias y la tuberculosis son las causas más frecuentes en los diagnósticos de tales derrames. Los métodos de laboratorio convencionales para el diagnóstico de tales derrames son ineficientes, porque los bacilos de la tuberculosis raramente se ven en los exámenes directos del líquido pleural. El presente estudio evalúa la interleucina-6, el interferón gamma (IFN-γ) y la adenosina desaminasa (ADA) como herramientas de diagnóstico en el derrame pleural. MÉTODOS: La interleucina-6, el IFN-γ, y la ADA fueron medidos en el líquido pleural de los pacientes con derrame pleural exudativo de origen tuberculoso, maligno y post-pneumónico, y el derrame pleural trasudativo de origen sistémico, con el fin de evaluar la utilidad diagnóstica de éstos. RESULTADOS: Los tres marcadores eran observables en todos los derrames, con niveles significativamente altos en los exudativos en comparación con los trasudativos. Se notó una diferencia estadísticamente significativa en los derrames de origen tuberculoso en comparación con los de origen maligno y postpneumónico, y los derrames pleurales trasudativos. CONCLUSIÓN: Llegamos a la conclusión de que los niveles de IL-6, IFN-Correspondence: Dr M Marie, College of Applied Medical Sciences, Clinical Laboratory Department, King Saud University, PO Box 10219, Riyadh 11433, Kingdom of Saudi Arabia. E-mail: drmmarie.2000@ gmail.com *Equally contributed to the manuscript YADA en el derrame pleural, son parámetros sensibles para diferenciar un derrame pleural exudado de uno trasudado, pudiendo por otra parte ayudar también a distinguir exudados de diferentes etiologías. Finalmente, los resultados sugieren que existe una diferencia notable en la forma en que se producen estos tres marcadores en los derrames efusiones pleurales exudativos en comparación con los derrames pleurales trasudativos.

Parameter estimation and use of gamma interferon assay for the diagnosis of bovine tuberculosis in Brazil / Estimação dos parâmetros e uso do teste do interferon gama para o diagnóstico da tuberculose bovina no Brasil

This study aimed to evaluate the interference of tuberculin test on the gamma-interferon (INFg) assay, to estimate the sensitivity and specificity of the INFg assay in Brazilian conditions, and to simulate multiple testing using the comparative tuberculin test and the INFg assay. Three hundred-fifty cattle from two TB-free and two TB-infected herds were submitted to the comparative tuberculin test and the INFg assay. The comparative tuberculin test was performed using avian and bovine PPD. The INFg assay was performed by the BovigamTM kit (CSL Veterinary, Australia), according to the manufacturer's specifications. Sensitivity and specificity of the INFg assay were assessed by a Bayesian latent class model. These diagnostic parameters were also estimate for multiple testing. The results of INFg assay on D0 and D3 after the comparative tuberculin test were compared by the McNemar's test and kappa statistics. Results of mean optical density from INFg assay on both days were similar. Sensitivity and specificity of the INFg assay showed results varying (95% confidence intervals) from 72 to 100% and 74 to 100% respectively. Sensitivity of parallel testing was over 97.5%, while specificity of serial testing was over 99.7%. The INFg assay proved to be a very useful diagnostic method.(AU)

O presente estudo avalia a interferência do teste de tuberculinização no teste do interferon gama (INFg), estima a sensibilidade e a especificidade do INFg em condições brasileiras e simula a utilização dos testes múltiplos usando a tuberculinização comparada e o teste do INFg. Trezentos e cinquenta animais oriundos de dois rebanhos livres e dois rebanhos positivos foram submetidos à tuberculinização comparada e ao teste de INFg. A tuberculinização comparada foi realizada utilizando PPD aviária e bovina. O teste de INFg foi realizado utilizando o kit Bovigam® (CSL Veterinary, Austrália) de acordo com as especificações do fabricante. A sensibilidade e especificidade do teste de INFg foram calculadas pelo Modelo Bayesiano de Classe Latente. Esses parâmetros foram também estimados para os testes múltiplos. Os resultados do teste de INFg no D0 e D3 após o teste de tuberculinização foram comparados pelos testes estatísticos de McNemar e kappa. Os resultados das médias de densidade ótica do teste de INFg em ambos os dias foram similares. A sensibilidade e a especificidade do teste de INFg apresentaram resultados variando (95% intervalo de confiança) de 72 a 100% e 74 a 100%, respectivamente. A sensibilidade do teste em paralelo foi acima de 97,5% enquanto a especificidade do teste em série foi acima de 99,7%. O teste do INFg provou ser um método de diagnóstico muito útil.(AU)

Expresión de IL-10, IL-4 e IFN- γ en lesiones activas de piel en niños con urticaria papular por picadura de pulga / Expression of IL-10, IL-4 and IFN-γ in active skin lesions of children with papular urticaria

Introducción. La urticaria papular por picadura de pulga se conoce como una enfermedad alérgica. Sin embargo, las investigaciones no muestran una clara relación con las enfermedades alérgicas. Objetivo. Estudiar la expresión de IL-10, IL-4 e IFN-γ, como marcadores de la respuesta efectora de células T en lesiones de piel de pacientes con urticaria papular por picadura de pulga. Materiales y métodos. Se incluyeron 14 biopsias de lesiones de piel de niños con diagnóstico de urticaria papular por picadura de pulga y 5 biopsias de piel sana obtenidas de niños sometidos a cirugía por enfermedades no inflamatorias. Todas las muestras se obtuvieron de niños menores de 12 años. Se extrajo ARN con trizol y se cuantificaron los niveles de expresión de las citocinas con la técnica de reacción en cadena de la polimerasa en tiempo real. Resultados. En los pacientes con urticaria papular por picadura de pulga, se encontró amplia diversidad en los niveles de expresión de IFN-γ e IL-10, y valores bajos constantes para IL-4. Se observaron tres perfiles que no corresponden a un patrón común en los pacientes. Las muestras obtenidas de tejidos sanos no presentaron expresión de las citocinas. Conclusiones. Los datos corresponden a la primera descripción de citocinas que median la respuesta inmunitaria en el sitio de la lesión cutánea en niños con con urticaria papular por picadura de pulga, lo cual indica que la respuesta local es mixta ya que no se encuentra predominio de un fenotipo específico en ninguno de los pacientes.

Introduction: Papular urticaria caused by the bites of fleas traditionally has been defined as a chronic allergic disease. However, currently no clear relationship has been described between this pathology and common allergic diseases. Objective: The expression of IL-10, IL-4 and IFN-γ as markers of effector T cell responses was examined in skin lesions of patients with papular urticaria by flea bite. Materials and methods: Fourteen skin lesion biopsies were sampled from children with a clinical diagnosis of papular urticaria by flea bite and were compared with 5 healthy skin biopsies of children with no history of the disease. All children were under 12 years old. RNA was extracted with trizol and the expression levels of cytokines were analyzed by real time PCR technique. Results: A wide range in the expression levels of IFN-γ and IL-10 was noted as well as constant low values of IL-4. Three distinct profiles were observed, but which did not correspond to a recognizable pattern among the patients. The samples obtained from healthy tissues showed no expression of any of the cytokines. Conclusions: This is the first characterization of cytokines that mediate the immune response at the site of the skin lesion in children with papular urticaria by flea bite. The data indicated that the local response was mixed and that a single phenotype is not predominant among the patients.

Interferón gamma recombinante como alternativa terapéutica en niños con artritis idiopática juvenil / Recombinant gamma Interferon as a therapeutical alternative in children with juvenile idiopathic arthritis

INTRODUCCIÓN. La artritis idiopática juvenil (AIJ) es una enfermedad del colágeno caracterizada por sinovitis crónica y síntomas extraarticulares, de inicio antes de los 16 años de edad. El interferón gamma (INFγ) mostró eficacia en un ensayo anterior con pacientes resistentes o intolerantes a las otras terapias disponibles, por lo que se decidió evaluar su eficacia y seguridad como medicamento modificador de la evolución de esta enfermedad. MÉTODOS. Se realizó un ensayo clínico abierto, no controlado, en el que se administró INFγ por vía intramuscular en dosis de 50 000 UI/kg (hasta 1 x 10(6) UI) durante 2 años. En el ensayo se incluyeron 20 pacientes con AIJ: 5 tenían la forma pauciarticular; 9, la poliarticular y 6, la sistémica. RESULTADOS. Al final del tratamiento, 13 pacientes (65 por ciento) se evaluaron como respondedores. El número de articulaciones afectadas, los síntomas sistémicos y los valores de eritrosedimentación y del cuestionario de calidad se redujeron significativamente. Igualmente disminuyó el número de pacientes que continuó consumiendo esteroides, así como la dosis de éstos. El tratamiento fue bien tolerado, excepto en 2 pacientes. CONCLUSIONES. El INFγ disminuye la expresión de la quimiocina CCR-4 en los niños, pero no en los adultos con la enfermedad. Es posible concluir que esta citocina puede ser una alternativa terapéutica eficaz en pacientes con AIJ; para confirmarlo se necesitan estudios controlados más extensos

INTRODUCTION: The juvenile idiopathic arthritis (JIA) is a collagen entity characterized by chronic synovitis and extra-articulation symptoms appearing before the 16 years old. Gamma Interferon (gamma-INF) showed its effectiveness in a prior trial with resistant and intolerant patients to other available gamma-INF therapies, thus authors assessed its effectiveness and safety as a modifier drug of the course of this entity. METHODS: An open clinical, no-controlled trial was carried out administering gammaINF by intramuscular route in doses of 50 000 IU/kg (up to 1 x 10(6) IU) during two years. Trial included 20 patients with JIA: five had the pauciarticular type; nine had the polyarticular one and six had the systemic one. RESULTS: At treatment termination, 13 patients (65 percent) were assessed as respondents. Figure of involved joints, the systemic symptoms and the erythrosedimentation values, and the quality questionnaire significantly decreased, as well as the figure of patients to continue consuming steroids and its dosage. Treatment was well tolerated, except 2 patients. CONCLUSIONS: Gamma-INF decrease the expression of CCR-4 chemokine in children, but not in adults ones presenting this entity. We conclude that this cytokine may be an efficient therapeutical alternative in patients with JIA; for its confirmation it is necessary more extent controlled studies

Experimental Study of Anti-hepatofibrotic Action of 18?-glycyrrhizic Acid in Rats / 中国药房

OBJECTIVE:To study the anti-hepatofibrotic action of 18?-glycyrrhizic acid(18?-GL) and gamma interferon (IFN-?) in rats METHODS:The rat model of liver fibrosis was induced by dimethyl nitrosamine(DMN),18?-GL or IFN-? was administrated before and 5 weeks after giving DMN,to prevent and treat liver fibrosis The pathological changes and degree of fibrosis in the liver were observed and compared with that of DMN control group RESUTLS:Compared to DMN control group,the collagen deposition in both 18?-GL and INF-? groups was significantly slight in degree(P

A Study on the Relationship of the Severity of Atopic Dermatitis, Serum IgE and IFN-gamma / 대한피부과학회지

BACKGROUND: Since the management of atopic dermatitis often needs prolonged administration of medication in children, laboratory index reflecting disease severity is necessary for optimal treatment of this disease. Immunoglobulin E (IgE) and gamma interferon (IFN-gamma) are some of the most important factors in the pathogenesis of atopic dermatitis. OBJECTIVE: This study was performed to find out if serum IFN-gamma together with IgE can be used as severity indices or disease markers of atopic dermatitis in Korean children. METHODS: A total of 14 patients and 6 normal controls were collected. The patients were evaluated for the symptoms and signs of the atopic dermatitis according to the criteria previously reported and classified into the mild and severe group. Blood samples were obtained and measured for serum IgE and IFN-gamma. RESULTS: Serum IFN-gamma levels of the patients with atopic dermatitis were decreased compared with those of normal control. However, patients in the severe atopic dermatitis group showed no significant difference from those in the mild group in terms of IFN-gamma levels. Serum IgE levels of the patients with atopic dermatitis were significantly increased compared with those of normal control. Moreover, patients from the severe atopic dermatitis group revealed higher IgE levels than those in the mild group. CONCLUSION: It was concluded that serum IgE can reflect severity of atopic dermatitis whereas serum IFN-gamma, which does not show significant difference between the mild and severe group, can only be used as a disease marker supplementing clinical features.

Effect of gamma-interferon on fibroblast proliferation and collagen synthesis after glaucoma filtering surgery in white rabbits

Failure of a glaucoma filtering operation mainly results from scarring at the filtering wound, and postoperative proliferation and migration of fibroblasts play an important role histologically in the formation of scar tissue. As an inhibitory agent for fibroblast proliferation, gamma-interferon has been introduced, and the application of gamma-interferon following filtering surgery is now being made on a trial basis. We studied the effect of gamma-interferon histologically on the fibroblast proliferation and collagen synthesis occurring at the filtering site by comparing the effect of gamma-interferon on the experimental group with that of 5-fluorouracil on the control group, using 10 rabbits (20 eyes) after posterior lip sclerectomy. Both groups showed similar flat and diffused bleb grossly and also showed a similar inhibitory effect on fibroblast proliferation and collagen fiber synthesis histologically. Our findings seem to justify the clinical use of gamma-interferon. Further studies on adequate dosage, method of administration, and local and systemic complications would be desired.

The Therapeutic Effect of Gamma Interferon in Advanced Renal Cell Carcinoma / 대한비뇨기과학회지

We evaluated the antitumor activity and toxicity of recombinant human interferon gamma (LBD -001) as a new modality for advanced renal cell carcinoma from March, 1988 to August, 1989 at the Department of Urology, St. Mary's Hospital, Catholic University Medical College. Eleven patients with advanced renal cell carcinoma were given recombinant gamma interferon at dose of 5.0-7.6 x 106U/day, subcutaneously three days per week. Among eleven patients, only one achieved partial response. Major adverse effects included fever, fatigue, myalgia and leukopenia, but no life threatening side effects were found. Although recombinant human interferon gamma have an antitumor activity against advanced renal cell carcinoma, further study is necessary to define the optimal treatment regimen.

Dynamic Changes in Collagen Type Ⅰ and Collagen Type Ⅲ in Rabbits Infected with Schistosoma japonicum and the Effect of Gamma Interferon * / 中国寄生虫学与寄生虫病杂志

Objective To observe the dynamic changes in collagen type Ⅰ and collagen type Ⅲ in rabbits with schistosomiasis japonica and the treatment effect of gamma interferon on the degradation of collagens in schistosomal hepatic fibrosis.Methods Each rabbit was infected with 80?1 S japonicum cercariae. Liver operations were done at different time points after infection and the liver specimens were embedded with paraffin and stained with ? SMA, HE and picric acid Sirius red. The stained slides were observed under polarizing microscope and different collagen areas calculated by computer imagine analysis system. At the 16th week after infection, the infected rabbits received a single dose of praziquantel and gamma interferon for 8 weeks.Results The area percent of collagen type Ⅰ at the 28th week after infection (40 14?17 00) increased about seven fold compared with the 8th week group (5 73?3 40). The area percent of collagen type Ⅲ at the 28th week after infection (6 80?5 19) increased about six fold compared with the 8th week group (1 15?1 34). The ? SMA positive cells also increased significantly. After gamma interferon treatment, the area percent of collagen type Ⅰ and type Ⅲ decreased significantly, from 18 51?7 52 and 4 63?3 64 (before treatment) to 3 09?1 54 and 0 40?0 37 (0 and 4 weeks after treatment) ( P

Gamma interferon modulates epidermal cell proliferation and mixed epidermal cell-lymphocyte reaction

Gamma interferon (gamma-IFN), a lymphokine produced by activated T lymphocytes, has a variety of effects on target cell. It induces class II antigens of the major histocompatibility complex not only in immunocompetent cells but also in non-immunocompetent cells. gamma-IFN also can exert, in addition to anti-viral activity, a series of anticellular effects on a variety of cell types. The effects of gamma-IFN on the proliferation of cultured epidermal cell (EC) and induction of HLA-DR antigen expression by EC (HLA-DR+KC) were studied. Furthermore, the immunologic role of HLA-DR+KC in the mixed epidermal cell-lymphocyte reaction (MECLR) was studied. The antiproliferative effect of gamma-IFN on the cultured EC was seen 3 days after treatment of gamma-IFN and the effect was dose-dependent. Number of HLA-DR+KC was increased dose-dependently with treatment of gamma-IFN. In MECLR, HLA-DR+KC had been found to exert stimulatory role on allogenic lymphocytes. However, there was no significant role of HLA-DR+KC on autologous lymphocytes.

Immunological unresponsiveness in leprosy and its relevance to immunoregulation in man.

The varied forms of leprosy form a clinical and immunological spectrum which offers extraordinary possibilities for insight into immunoregulatory mechanisms in man. At one pole, tuberculoid leprosy, patients develop high levels of cell-mediated immunity which ultimately results in killing of bacilli in the tissues, albeit often with damage to nerves. At the lepromatous pole, patients exhibit selective immunological unresponsiveness to antigens of Mycobacterium leprae. Even though all currently known protein species of Mycobacterium leprae and BCG are cross-reactive, lepromatous patients unreactive to Mycobacterium leprae antigens frequently respond strongly to tuberculin. In vitro experiments suggest the existence of lepromin-induced suppressor activity, mediated by both monocytes and Τ cells. The Τ suppressor cells have the T8 phenotype of which 50% express the activation markers, Ia and FcR. The one unique species of antigen of the leprosy bacillus is a phenolic glycolipid, and it appears that the Ts cells largely recognize the terminal trisaccharide of this unique antigen. Depletion of Ts cells restores in vitro reactivity of lymphocytes to lepromin in a portion of lepromatous patients, and addition of IL-2 containing supernatants partially restores responsiveness to Mycobacterium leprae antigens. Vaccination of lepromatous patients with a mixture of Mycobacterium leprae and live BCG restores cell-mediated immunity in the majority of lepromatous patients, and concomitantly reduces the in vitro suppressor activity and number of activated T8 cells. These experiments suggest the existence of stage-of-disease related suppressor cells in leprosy which appear to block the responsiveness of TH capable of responding to either specific or cross-reactive mycobacterial antigens. The mode of action of these Ts appears to be the inhibition of production of IL-2 and other lymphokines. Successful immunotherapeutic vaccination appears to overcome this block in the majority of patients.