There are strong evidences suggesting that Thl and Th2 lymphocytes develop from the same Thlymphocyte precursor under the influence of environmental or genetic factors acting at the level of antigen presentation, but it remains to be answered whether it is possible to change the cytokine profile of established or ongoing Th1 and Th2 response. The purpose of this study is to reveal whether it is possible to reverse the cytokine profile of human Th lymphocytes by the modulation of antigen presentation. Using a multiparameter flow cytometric assay that allows simultaneous determination of surface CD4 and intracellular IFN-r or IL-4, we have studied the emergence of Th1 or Th2 lymphocytes in response to tetanus toxoid exposure and the patterns of cytokine synthesis in established T lymphocyte clones. Th2 populations arising after 4 wk of stimulation in IL-2, PHA, tetanus toxoid and irradiated autogeneic peripheral blood mononuclear cells as antigen presenting cells (APC) could give rise to IFN-r-producing Th1 lymphocytes when stimulated in IL-2 plus PHA in the absence of antigen and APC. These IFN-r-producing Th1 lymphocytes nearly disappeared and IL-4-producing Th2 lymphocytes predominated again when cultured again in the presence of antigen and APC. In contrast, prolonged culture in the absence of antigen and APC induced relative predominance of IFN-r-producing The lymphocytes. The cytokine profile of long-term Th2 population arising originally from the repeated stimulation in the presence of antigen and APC appeared more homogeneous and less reversible, although they could convert to Th1 lymphocytes when cultured without antigen and APC. These findings may explain that the polarized Th response is reversible depending on the presence of antigen presentation.
Antigen Presentation* ; Antigen-Presenting Cells ; Clone Cells ; Humans ; Interleukin-2 ; Interleukin-4 ; Lymphocytes ; T-Lymphocytes, Helper-Inducer* ; Tetanus Toxoid

BACKGROUND: Allergen-specific immunotherapy ( IT ) can be an important adjunctive therapy in the treatment of allergic disorders. Although a number of studies have shown that cytokine production by T cells may be modified by IT, IT-induced chsnges at the single cell level in allergen -specific Th ( T helper ) and Tc ( cytotoxic T ) responses have not been reported. Objective : The objectives of the present study were ( 1 ) to demonstrate differences in the house dust mite(HDM)-induced cytokine production patterns of Th and Tc cells between untreated and treated HDM allergic patients and ( 2 ) to determine whether there are differences between child and adult patients in Th and Tc cell responses to HDM. METHOD: This study included twenty Dermatophagoides farinae (Df)-sensitive asthmatics ( ten children and ten adults ), of which five children and five adults received immunotherapy to Df over a 1.5- to 3-year period. Peripheral blood mononuclear cells ( PBMC ) were isolated from peripheral blood of each patient and cultured in the presence of IL-2 ( 10ng/ml ) and Df extract (100ug/ml) for 6 days. After harvesting cultured cells, Th and Tc cell frequencies were determined by a multiparameter cytokine flow cytometric assay that allows simultaneous determination of intracellular IFN-r and IL-4 in CD4+ or CD8+ cells. RESULTS: Predominant Th2 responses to Df were observed in all untreated child patients, three untreated adult patients, and two treated adult patients. On the other hand, predominant Thl responses to Df were observed in all treated child patients, two of untreated adult patients, and three of treated adult patients. Predominant Tcl responses to Df were observed in all groups of patients. However, Tcl responses were more prominent in adults than in children and in treated adult patients than in untreated adult patients. In children, there were no differences in predominant Tcl responses except in one treated child, in whom more prominent Tcl response was observed.
Adult ; Cells, Cultured ; Child ; Dermatophagoides farinae ; Dust ; Hand ; Humans ; Immunotherapy* ; Interleukin-2 ; Interleukin-4 ; T-Lymphocytes

OBJECTIVE: The purpose of this study was to analyse clinical manifestations and laboratory findings in childhood patients with polyarticularonset juvenile rheumatoid arthritis (JRA). METHODS: Eleven cases of polyarticular JRA who were diagnosed and treated in the Department of Pediatrics, Seoul National University Children's Hospital from June 1988 to May 1995 were investigated for clinical manifestations and laboratory findings. RESULTS: 1) There were 6 males and 5 females and their ages of onset were 4 years to 15.1 years(mean 10.9 years). 2) Systemic manifestations were not observed, but low-grade fever was noted in 5 patients. 3) The involvement of joints was symmetric in 9 patients and asymmetric in 2 patients. 4) The most commonly affected joints were knees and ankles, followed by proximal interphalangeal joints of hand, shoulder, elbow, temporomandibular joint, and other joints. 5) Roentgenographic changes of joints were detected in 6 patients and bone scan in 7 patients showed increased uptake in the involved joints. 6) The main laboratory findings observed were microcytic and hypochromic anemia (64%), thrombocytosis (82%), elevated eryhtrocyte sedimentation rate (100%), positive or increased C-reactive protein(100%), positive rheumatoid factor(RF) (18%), positive antinuclear antibody(ANA) (27%). RF was positive in 2 girls with later age of onset and the pattern of immunofluorescent ANA were all homogeneous. 7) Nonsteroid antiinflammatory drugs (NSAIDs) were used most frequently and steroid with or without sulfasalazine was tried in 4 patients unresponsive to NSAIDs. 8) At last follow-up, 6 cases(55%) were classified as functional class I, 4 cases(36%) as class II, and 1 case(9%) as class III. CONCLUSION: These data showed the clinical manifestations and laboratory findings of polyarticularonset juvenile rheumatoid arthritis in Korean children.
Age of Onset ; Anemia, Hypochromic ; Ankle ; Anti-Inflammatory Agents, Non-Steroidal ; Arthritis, Juvenile* ; Child ; Elbow ; Female ; Fever ; Follow-Up Studies ; Hand ; Humans ; Joints ; Knee ; Male ; Pediatrics ; Seoul ; Shoulder ; Sulfasalazine ; Temporomandibular Joint ; Thrombocytosis

There were many instances in which glaucoma, esp. primary, combined with hearing disturbance. The etiology of these cases has not been known until now. We had 15 primary glaucoma patients for whom pure tone audiometry wa~ performed, and could find the hearing defect in high tone in 5 cases (1/3 among those patients). The audiometric curve was similar to that in the presbycusis, but severer in degree than that occured within the normal physiological aging process. The average age was 62.4 year in the group with the hearing defect, and 45.6 year in the group without the hearing defect. There were no relationship between the hearing defect and intraocular tension, visual field change, glaucomatous cupping, and duration of glaucoma. These results may support the opinion of the authors that the hearing disturbance in glaucomatous patients is related to the arterioscIerotic changes which aggrevate the presbycusis, and not related to glaucoma itself. On the otherhand, however, it is stilI impossible for us to rule out that the pleiotropic and multifactorial genetic factors may play as a common important role in the hearing disturbances and glaucoma. And further studies would be necessary for these problems.
Aging ; Audiometry ; Glaucoma* ; Hearing* ; Humans ; Presbycusis ; Visual Fields

PURPOSE: The purpose of this study was to observe the effect of IFN- and PGE2 on TNF- production by human peripheral mononuclear cells(PBMC) that were stimulated with LPS. METHODS: PBMC were separated by Ficoll-Hypaque gradient centrifugation from human peripheral venous blood and were incubated for 72 hours with or without LPS, IFN- , PGE2, and indomethacin according to various conditions. TNF- activity of PBMC culture supernatants was assayed by determining the cytotoxicity against L929 cells. RESULTS: 1) The production of TNF- by PBMC in response to LPS reached the highest level between 8-24 hours and returned to control level by 72 hours. 2) When IFN- was added together with LPS, LPS-induced TNF- production was enhanced and prolonged, which was more remarkable when IFN- was added at higher concentration or earlier than LPS. 3) When PGE2 was added together with LPS, LPS-induced TNF- production was suppressed. 4) The addition of IFN-gamma reduced the suppressive effect of PGE2 on LPS-induced TNF- production. 5) Enough amount of indomethacin enhanced production of TNF- by LPS. CONCLUSIONS: IFN-gamma increased and PGE2 decreased the production of TNF- by PBMC which were stimulated with LPS. And PBMC which were pretreated with IFN-gamma were resistent to the suppressive effect of PGE2.
Centrifugation ; Dinoprostone* ; Humans* ; Indomethacin

PURPOSE: The purpose of this study is to determine IFN-gamma and IL-4 production patterns of individual Th lymphocytes in various in vivo and in vitro conditions by cytokine flow cytometry. METHODS: Using a multiparameter flow cytometric assay that allows simultaneous determination of surface CD4 and intracellular IFN-gamma or IL-4, we studied the emergence of Th1 or Th2 lymphocytes in peripheral blood mononuclear cells (PBMC) which were incubated under the influence of various stimuli for Th1/Th2 polarization or steroid. The same analysis was performed for PBMC from six healthy donors (three children and three adults) and three asthmatic children before and after rush immunotherapy. RESULTS: Dominant Th2 lymphocytes arised from IL-2-stimulated PBMC in spite of dominant production of IFN-gamma in the supernatant, but the addition of IL-12 and/or IFN-gammainduced increased emergence of Th0 and Th1 lymphocytes. Steroid could not modify ongoing Th2 response arising from D. farinae or tetanus toxoid-stimulated PBMC. IFN-gamma-producing Th1 lymphocytes predominated over IL-4-producing Th2 lymphocytes in peripheral blood isolated from three healthy adults and three healthy children, which was also demonstrated in three children with allergic asthma. The early changes in peripheral Th lymphocytes after immunotherapy on asthmatic children were reduced frequency of IFN-gamma-producing Th1 lymphocytes and increased frequency of IL-4-producing Th2 lymphocytes. CONCLUSION: We conclude that detection of intracellular cytokines by flow cytometry is an easy and specific method which may be used to study single cells in heterogeneous populations as well as to observe cytokine patterns of homogeneous cells. And the direct visualization of T cell effector responses shown by this flow cytometric approach allows the opportunity to evaluate the participation of Th cells in various human diseases.
Adult ; Asthma ; Child ; Cytokines ; Flow Cytometry* ; Humans ; Immunotherapy ; Interferon-gamma ; Interleukin-12 ; Interleukin-4 ; Lymphocytes* ; Tetanus ; Tissue Donors

PURPOSE: The purpose of this study was to analyse clinical and laboratory patterns in patients in Korea with juvenile Rheumatoid Arthritis(JRA), pauciarticular type and to know the characteristics of pauciarticular JRA in Korea. METHODS: Twenty-three cases of pauciarticular juvenile rheumatoid arthritis(JRA) who were diagnosed in the department of Pediatrics, Seoul National University hospital (from june 1988 to May 1994) were reviewed. RESULTS: 1) There were 17 males and 6 females, their ages of onset were 3 years to 13 years(mean 7.3 years). 2) Knee joint was involved most frequently, and there was predominant involvement in the lower extrimities(21 patients). There were five cases that shifted to polyarticular type. 3) Two male patients were diagnosed to have iridocyclitis and treated with topical steroid without problems. 4) HLA-B27 was found in 7 male patients. 5) Low hemoglobin level was noted in three cases, platelet count was elevated in nine cases and white blood cell count was within normal range in all cases. Elevated ESR was noted in 19 cases(83%) and CRP was positive in 15 cases(65%). RF(rheumatoid factor)was positive in 1 cases and 5 cases(22%) were detected as ANA(antinuclear antibody)-positive. 6) Frequent radiological findings of arthritis were joint space narrowing, soft tissue swelling, osteopenia, osteoporosis, remodeling of joint space, and subchondral erosions. In bone scan, increased uptake in the involved joints was detected in five cases. 7) NSAIDs(nonsteroid antiinflammatory durgs) was used most freuently, and steroid was prescribed in nine patients who responded poorly to NSAIDs. 8) At onset, 21 cases (91%) were classified as functional class II and 2 cases(9%) were classified as functional class III. At last follow-up, 5 cases(22%) were classified as functional class I, 11 cases(48%) were classified as functional class II, and 7 cases(30%) were classified as functional class III. CONCLUSIONS: We evaluated clinical manifestation, disease course, and laboratory findings of 23 Korean children with pauciarticular juvenile rheumatoid arthritis. Patients were classified in functional class, which tended to be poorer in children with a polyarthric course.
Anti-Inflammatory Agents, Non-Steroidal ; Arthritis ; Arthritis, Juvenile ; Bone Diseases, Metabolic ; Child ; Female ; Follow-Up Studies ; HLA-B27 Antigen ; Humans ; Iridocyclitis ; Joints ; Knee Joint ; Korea ; Leukocyte Count ; Male ; Osteoporosis ; Pediatrics ; Platelet Count ; Reference Values ; Seoul

Juvenile rheumatoid arthritis (JRA) is the most common rheumatic childhood disease; its onset is before 16 years of age and it persists for at least 6 weeks. JRA encompasses a heterogeneous group of diseases that is classified according to 3 major presentations: oligoarthritis, polyarthritis, and systemic onset diseases. These presentations may originate from the same or different causes that involve interaction with specific immunogenetic predispositions, and result in heterogeneous clinical manifestations. An arthritic joint exhibits cardinal signs of joint inflammation, such as swelling, pain, heat, and loss of function; any joint can be arthritic, but large joints are more frequently affected. Extra-articular manifestations include high fever, skin rash, serositis, and uveitis. The first 2 types of JRA are regarded as T helper 1 (Th1) cell-mediated inflammatory disorders, mainly based on the abundance of activated Th1 cells in the inflamed synovium and the pathogenetic role of proinflammatory cytokines that are mainly produced by Th1 cell-stimulated monocytes. In contrast, the pathogenesis of systemic onset disease differs from that of other types of JRA in several respects, including the lack of association with human leukocyte antigen type and the absence of autoantibodies or autoreactive T cells. Although the precise mechanism that leads to JRA remains unclear, proinflammatory cytokines are thought to be responsible for at least part of the clinical symptoms in all JRA types. The effectiveness of biologic therapy in blocking the action of these cytokines in JRA patients provides strong evidence that they play a fundamental role in JRA inflammation.
Arthritis ; Arthritis, Juvenile Rheumatoid ; Autoantibodies ; Biological Therapy ; Child ; Cytokines ; Exanthema ; Fever ; Hot Temperature ; Humans ; Immunogenetics ; Inflammation ; Joints ; Leukocytes ; Monocytes ; Serositis ; Synovial Membrane ; T-Lymphocytes ; Th1 Cells ; Uveitis

Experimental replacements of rabbit vitreous by air, normal saline, dextran and Haemaccel were tried in albino rabbits. After aspiration of 0.7ml of liquid vitreous from the central portion of vitreous, 0.5ml of substitutes were injected. Clinically, these substitutes were well tolerated with slight uveal inflammation which subsided within one week. Intraocular pussure returned to normal value after 5 days. Hexosamine content of the whole vitreous samples showed moderate increase after Haemaccel injection which decreased slowly thereafter, whereas no significant changes were observed with other substitutes. Hydroxyproline content of the whole vitreous also showed marked increase after injection of Haemaccel, owing to the high hydroxyproline content of HaemacceJ. After 6 weeks 22.9% of the injected hydroxyproline remained in the vitreous. With other substitutes no change was observed.
Dextrans ; Hydroxyproline ; Inflammation ; Polygeline ; Rabbits ; Reference Values

Exhaled nitric oxide (NO) has been extensively investigated as a noninvasive marker of airway inflammation in asthma. The increased NO expression induced by inflammatory mediators in airways can be monitored easily in exhaled air from asthmatic children. Based on the relationship between the increased NO expression and eosinophilic airway inflammation, fractional exhaled nitric oxide (FeNO) measurements become an important adjunct for the evaluation of asthma. In addition, the availability of portable devices makes it possible to measure FeNO more easily and frequently in the routine pediatric practice. Despite various confounding factors affecting its levels, FeNO can be applicable in diagnosing asthma, monitoring treatment response, evaluating asthma control, and predicting asthma exacerbations. Thus, although pulmonary function tests are the standard tools for objective measurements of asthmatic control, FeNO can broaden the way of asthma monitoring and supplement standard clinical asthma care guidelines.
Asthma* ; Breath Tests ; Child ; Eosinophils ; Humans ; Inflammation ; Nitric Oxide* ; Respiratory Function Tests