Macrophage Activation Syndrome Triggered by Herpes Viral Infection as the Presenting Manifestation of Juvenile Systemic Lupus Erythematosus

Macrophage activation syndrome (MAS) is a rare complication in systemic lupus erythematosus (SLE) that can be triggered by infections. Due to the fact that MAS may mimic clinical features of underlying rheumatic disease, or be confused with an infectious complication, its detection can prove challenging. This is particularly true when there is an unknown/undiagnosed disease; and could turn into an even greater challenge if MAS and SLE are combined with a viral infection. A-14-year-old female came to the hospital with an ongoing fever for 2 weeks and a painful facial skin rash. Hepatomegaly, pancytopenia, increased aspartate aminotransferase, elevated serum ferritin and lactate dehydrogenase were reported. No hemophagocytic infiltration of bone marrow was reported. The patient was suspected for hemophagocytic lymphohistiocytosis. Her skin rashes were eczema herpeticum, which is usually associated with immune compromised conditions. With the history of oral ulcers and malar rash, positive ANA and low C3, C4 and the evidence of hemolytic anemia, she was diagnosed as SLE. According to the diagnostic guideline for MAS in SLE, she was diagnosed MAS as well, activated by acute HSV infection. After administering steroids and antiviral agent, the fever and skin rash disappeared, and the abnormal laboratory findings normalized. Therefore, we are reporting a rare case of MAS triggered by acute HSV infection as the first manifestation of SLE.

Evaluation of Tuberculosis Activity in Patients with Anthracofibrosis by Use of Serum Levels of IL-2 sRalpha, IFN-gamma and TBGL(Tuberculous Glycolipid) Antibody / 결핵

BACKGROUND: Anthracofibrosis, a descriptive term for multiple black pigmentation with fibrosis on bronchoscopic examination, has a close relationship with active tuberculosis (TB). However, TB activity is determined in the later stage by the TB culture results in some cases of anthracofibrosis. Therefore, it is necessary to identify early markers of TB activity in anthracofibrosis. There have been several reports investigating the serum levels of IL-2 sRalpha, IFN-gamma and TBGL antibody for the evaluation of TB activity. In the present study, we tried to measure the above mentioned serologic markers for the evaluation of TB activity in patients with anthracofibrosis. METHODS: Anthracofibrosis was defined when there was deep pigmentation (in more than two lobar bronchi) and fibrotic stenosis of the bronchi on bronchoscopic examination. The serum of patients with anthracofibrosis was collected and stored under refrigeration before the start of anti-TB medication. The serum of healthy volunteers (N=16), patients with active TB prior to (N=22), and after (N=13), 6 month-medication was also collected and stored. Serum IL-2 sRalpha and IFN-gamma were measured with ELISA kit (R&D system, USA) and serum TBGL antibody was measured with TBGL EIA kit (Kyowa Inc, Japan). RESULTS: Serum levels of IL-2 sRalpha in healthy volunteers, active TB patients before and after medication, and patients with anthracofibrosis were 640+/-174, 1,611+/-2,423, 953+/-562, and 863+/-401 pg/ml, respectively. The serum IFN-gamma levels were 0, 8.16+/-17.34, 0.70+/-2.53, and 2.33+/-6.67 pg/ml, and TBGL antibody levels were 0.83+/-0.80, 5.91+/-6.71, 6.86+/-6.85, and 3.22+/-2.59 U/ml, respectively. The serum level of TBGL antibody was lower than that of other groups (p<0.05). There was no significant difference of serum IL-2 sRalpha and IFN-gamma levels among the four groups. CONCLUSION: The serum levels of IL-2 sRalpha, IFN-gamma and TBGL antibody were not useful in the evaluation of TB activity in patients with anthracofibrosis. More useful ways need to be developed for the differentiation of active TB in patients with anthracofibrosis.

The Relationship Between the NF-kappa B Activity and Anti-inflammatory Action of Surfactant in the Acute Lung Injury of Rats / 결핵

BACKGROUND: The therapeutic effects of surfactants on acute lung injury derive not only from their recruiting action on collapsed alveoli but also from their anti-inflammatory action in the alveolar space. This study evaluated the anti-inflammatory action of a surfactant in an acute lung injury model of rats by measuring the WBC count, IL-1beta and IL-6 level of bronchoalveolar lavage(BAL) fluid. In addition, neutrophils were recollected from the BAL fluid and the NF-kappa B activity of the neutrophilic nuclear protein was evaluated. METHODS: Male Sprague-Dawley rats weighing approximately 300 gram were divided into 3 groups, which consisted of 6 rats respectively. In the control group, normal saline(3ml/kg) was instilled into the trachea twice with 30 minute interval. In two other groups, acute lung injury was induced by the intra-tracheal instillation of LPS(5mg/kg). Thirty minutes later, either a surfactant(ST group; 30mg/kg) or normal saline(NT group: 3ml/kg) was instilled via the trachea. Twenty-four hours after the LPS instillation, the BAL fluid was retrieved to measure the WBC count and cytokine(IL-1beta and IL-6) levels. The neutrophils were isolated from the BAL fluid and the nuclear protein was extracted to evaluate the NF-kappa Bactivity using a eletrophoretic mobility shift assay(EMSA). RESULTS: The WBC count of the BAL fluid of the ST group(3,221+/-1,914 X 10(3)/micro liter) was higher than that of the control group(356+/-275X10(3)/micro liter)(p<0.05) and lower than that of the NT group(5,561+/-1,757 X 10(3)/micro liter)(p<0.05)). The BAL fluid level of IL-1beta from the NT group(2,064+/-1,082pg/ml) was higher than those of the ST group(360+/-234pg/ml)(p<0.05) and the control group(0pg/ml)(p<0.05). The BAL fluid concentration of IL-6 from the NT group(3,621+/-567pg/ml) was also higher than those of the ST group(1,754+/-1,340pg/ml)(p<0.05) and control group(49+/-62pg/ml)(p<0.05). The NF-kappa B activity of the neutrophilic nuclear protein in the ST group and NT group was similar. CONCLUSIONS: The surfactant attenuates the alveolar inflammation in the acute lung injury of rats model. However, its anti-inflammatory action does no't appear to be mediated by the inhibition of NF-kappa B activity.

The Effects of Surfactant on Neutrophil Apoptosis in Lipopolysaccharide Induced Acute Lung Injury in Rat / 결핵

BACKGROUND: The therapeutic effects of surfactant on acute lung injury derive not only from its recruiting action on collapsed alveoli but also from its anti-inflammatory effects. Pro-apoptotic action on alveolar neutrophils represents one of the important anti-inflammatory mechanisms of surfactant. In the present study, we evaluated the effects of surfactant on the apoptosis of human peripheral and rat alveolar neutrophils. METHODS: In the (Ed- the article is not definitely needed but it helps to separate the two prepositions 'in') in vitro study, human neutrophils were collected from healthy volunteers. An equal number of neutrophils (1X10(6)) (Ed-confirm) was treated with LPS (10, 100, 1000ng/ml), surfactant (10, 100, 1000micro gram/ml), or a combination of LPS (1000ng/ml) and surfactant (10, 100, 1000micro gram/ml). After incubation for 24 hours, the apoptosis of neutrophils was evaluated by Annexin V method. In the in vivo study, induction of acute lung injury in SD rats by intra-tracheal instillation of LPS (5mg/kg) was followed by intra-tracheal administration of either surfactant (30mg/kg) or normal saline (5ml/kg). Twenty-four hours after LPS instillation, alveolar neutrophils were collected and the apoptotic rate was evaluated by Annexin V method. In addition, changes of the respiratory mechanics of rats (respiratory rate, tidal volume, and airway resistance) were evaluated with one chamber body plethysmography before, and 23 hours after, LPS instillation. RESULTS: In the in vitro study, LPS treatment decreased the apoptosis of human peripheral blood neutrophils (control; 47.4+/-5.0%, LPS 10ng/ml; 30.6+/-10.8%, LPS 100ng/ml; 27.5+/-9.5%, LPS 1000ng/ml; 24.4+/-7.7%). The combination of low to moderate doses of surfactant with LPS promoted apoptosis (LPS 1000ng/ml + Surf 10micro gram/ml; 36.6+/-11.3%, LPS 1000ng/ml + Surf 100micro gram/ml; 41.3+/-11.2%). The high dose of surfactant (1000micro gram/ml) decreased apoptosis (24.4+/-7.7%) and augmented the anti-apoptotic effect of LPS (LPS 1000ng/ml + Surf 1000micro gram/ml; 19.8+/-5.4%). In the in vivo study, the apoptotic rate of alveolar neutrophils of surfactant-treated rats was higher than that of normal saline-treated rats (6.03+/-3.36% vs. 2.95+/-0.58%). The airway resistance (represented by Penh) of surfactant-treated rats was lower than that of normal saline-treated rats at 23 hours after LPS injury (2.64+/-0.69 vs. 4.51+/-2.24, p<0.05). CONCLUSIONS: Surfactant promotes the apoptosis of human peripheral blood and rat alveolar neutrophils. Pro-apoptotic action on neutrophils represents one of the important anti-inflammatory mechanisms of surfactant.