This study was performed to observe the therapeutic effects of interferon-gamma(IFN-gamma) and gamma-globulin(gamma-globulin) in experimental Pneumocystis carinii pneumonia of immune suppressed mice. After 9 weeks, trimethoprim-sulfamethoxazole(TMP-SMZ; 10-50 mg/mouse/day), mouse IFN-gamma(5 x 10(4) units/mouse/day) and mouse gamma-globulin(20 mg/mouse/day) were administered to the mice for 3 weeks by the experimental group. The therapeutic efficacy was evaluated by body weights, histopathologic and electron microscopic findings of the lungs, and number of P. carinii cysts by Gomori's methenamine silver stain. Body weights of the mice were significantly increased in the group of combination therapy of TMP-SMZ with IFN-gamma or gamma-globulin, and in the group of TMP-SMZ treatment (p < 0.05), however, little effect was found in the group of gamma-globulin alone. Histopathologic findings of P. carinii pneumonia were much improved in the group of combination therapy of TMP-SMZ with IFN-gamma. Treatment with either TMP-SMZ or IFN-gamma significantly reduced the number of cysts in the P. carinii pneumonia, but gamma-globulin alone was ineffective. In electron microscopic findings of P. carinii pneumonia, the number of trophozoites and cysts were reduced by treatment with either TMP-SMZ or IFN-gamma, and most of the cysts were empty or containing one or two intracystic bodies. The present results suggested, that combination therapy of TMP-SMZ with IFN-gamma had synergistic effects in treatment of P. carinii pneumonia in experimental mice.
Drug-Synergism ; Drug-Therapy,-Combination ; English-Abstract ; Gamma-Globulins-administration-and-dosage ; Interferon-Type-II-administration-and-dosage ; Mice- ; Trimethoprim-Sulfamethoxazole-Combination-administration-and-dosage ; *Gamma-Globulins-therapeutic-use ; *Interferon-Type-II-therapeutic-use ; *Pneumonia,-Pneumocystis-carinii-therapy ; Gamma-Globulins ; Trimethoprim-Sulfamethoxazole-Combination ; Interferon-Type-II

The aim of this study was to investigate the adjuvant effects of interferon-gamma (IFN-gamma) inhalation therapy for six months in the treatment of refractory multidrug-resistant pulmonary tuberculosis (MDR-TB). Aerosolized IFN-gamma was given to six MDRTB patients with persistent positive smears and cultures despite long-term medical treatment. The patients received aerosolized two million international units of IFNthree times a week for 6 months while they continued on identical antituberculous chemotherapy. Before IFN-gamma inhalation therapy, the patients received a median of 6.5 (range, 4 to 7) antituberculous drugs for median duration of 29 months (range,7 to 76). After IFN-gamma inhalation therapy, sputum smears remained persistently positive in all patients throughout the study period. Sputum cultures were transiently negative at the 4th month in two patients, but became positive again at the end of 6 months of IFN-gamma therapy. Five patients had radiological improvement including three patients who showed a decrease in the size of the cavitary lesions. Resectional surgery could be performed in one patient in whom substantial clinical and radiological improvement was noted after IFN-gamma inhalation therapy. These results suggest that IFN-gamma inhalation therapy may be effective for some cases of refractory MDR-TB who are otherwise not responding to conventional therapy.
Administration, Inhalation ; Adult ; Antineoplastic Agents/*administration & dosage ; Antitubercular Agents/therapeutic use ; Drug Resistance, Bacterial ; Drug Resistance, Multiple ; Drug Therapy, Combination ; Female ; Human ; Interferon Type II/*administration & dosage ; Male ; Middle Aged ; Support, Non-U.S. Gov't ; Tuberculosis, Pulmonary/*drug therapy/radiography

OBJECTIVETo investigate the effects of oral administration of type II collagen (CII) on adjuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CII with those of the Chinese traditional medicine Tripterygium Polyglycoside administered similarly.

METHODSArthritis was induced in rats by immunization using Freund's complete adjuvant (FCA). After feeding rats either soluble CII or Tripterygium Polyglycoside, changes in degree of articular swelling and articular histological findings were observed in AA rats. Some correlative immunological indexes were measured, including delayed type hypersensitivity (DTH) reaction, anti-collagen and anti-Mycobacterium tuberculosis (MT) antibody in serum, and levels of IFN-gamma and TNF-alpha in articular steep in rats.

RESULTSOral administration of CII was able to alleviate both distinctly articular and general symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule. The effects brought about by CII were stronger than those by Tripterygium Polyglycoside. Oral administration of CII inhibited antigen-specific immune response, such as DTH and antibody reaction to CII. In addition, the expression of IFN-gamma and TNF-alpha in joints were locally downregulated.

CONCLUSIONSThe therapeutic effect of oral administration of CII is obvious on adjuvant arthritis in rats. Its remedial mechanisms are likely related to the downregulation of both IFN-gamma and TNF-alpha, and the suppression of cell immunity.

Administration, Oral ; Animals ; Antibodies ; blood ; Arthritis, Experimental ; drug therapy ; immunology ; Collagen Type II ; therapeutic use ; Hypersensitivity, Delayed ; prevention & control ; Immune Tolerance ; Interferon-gamma ; biosynthesis ; Male ; Mycobacterium tuberculosis ; immunology ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane ; pathology ; Tripterygium ; Tumor Necrosis Factor-alpha ; biosynthesis

Food allergies affect about 4% of the Korean population, and buckwheat allergy is one of the most severe food allergies in Korea. The purpose of the present study was to develop a murine model of IgE-mediated buckwheat hypersensitivity induced by intragastric sensitization. Young female C3H/HeJ mice were sensitized and challenged intragastricly with fresh buckwheat flour (1, 5, 25 mg/dose of proteins) mixed in cholera toxin, followed by intragastric challenge. Anaphylactic reactions, antigen-specific antibodies, splenocytes proliferation assays and cytokine productions were evaluated. Oral buckwheat challenges of sensitized mice provoked anaphylactic reactions such as severe scratch, perioral/periorbital swellings, or decreased activity. Reactions were associated with elevated levels of buckwheatspecific IgE antibodies. Splenocytes from buckwheat allergic mice exhibited significantly greater proliferative responses to buckwheat than non-allergic mice. Buckwheat-stimulated IL-4, IL-5, and INF-gamma productions were associated with elevated levels of buckwheat-specific IgE in sensitized mice. In this model, 1 mg and 5 mg dose of sensitization produced almost the same degree of Th2-directed immune response, however, a 25 mg dose showed blunted antibody responses. In conclusion, we developed IgE-mediated buckwheat allergy by intragastric sensitization and challenge, and this model could provide a good tool for future studies.
Anaphylaxis/blood/immunology ; Animals ; Cell Proliferation/drug effects ; Comparative Study ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Fagopyrum/*immunology ; Female ; *Flour ; Food Hypersensitivity/blood/*immunology ; Immunoglobulin E/blood/immunology ; Immunoglobulin G/blood/immunology ; Interferon Type II/biosynthesis ; Interleukin-4/biosynthesis ; Interleukin-5/biosynthesis ; Mice ; Mice, Inbred C3H ; Plant Extracts/administration & dosage/immunology ; Research Support, Non-U.S. Gov't ; Spleen/cytology/drug effects/metabolism ; Stomach/drug effects/*immunology ; T-Lymphocytes/cytology/drug effects/metabolism ; Time Factors