Rheumatological manifestations in patients with melioidosis.

Melioidosis, an infection caused by the bacterium Burkholderia pseudomallei, has a wide range of clinical manifestations. Here, we describe rheumatological melioidosis (involving one or more of joint, bone or muscle), and compare features and outcome with patients without rheumatological involvement. A retrospective study of patients with culture-confirmed melioidosis admitted to Sappasithiprasong Hospital, Ubon Ratchathani during 2002 and 2005 identified 679 patients with melioidosis, of whom 98 (14.4%) had rheumatological melioidosis involving joint (n=52), bone (n = 5), or muscle (n = 12), or a combination of these (n=29). Females were over-represented in the rheumatological group, and diabetes and thalassemia were independent risk factors for rheumatological involvement (OR; 2.49 and 9.56, respectively). Patients with rheumatological involvement had a more chronic course, as reflected by a longer fever clearance time (13 vs 7 days, p = 0.06) and hospitalization (22 vs 14 days, p < 0.001), but lower mortality (28% vs 44%, p = 0.005). Patients with signs and symptoms of septic arthritis for longer than 2 weeks were more likely to have extensive infection of adjacent bone and muscle, particularly in diabetic patients. Surgical intervention was associated with a survival benefit, bur not a shortening of the course of infection.

The modulatory effect of antigen- and PAF-induced asthmatic reaction by aerosol administration of OKY-046 in guinea pigs.

The therapeutic effect of a thromboxane A2 (TXA2) synthetase inhibitor on asthma is still controversial. This study was aimed at clarifying its effect on asthmatic reactions in guinea pigs. Both ovalbumin (OVA)- and platelet activating factor (PAF)-induced dual phase airway spasm and hyperreactivity in guinea pigs were used as the asthma model. Our results demonstrated that aerosol administration of OKY-046 could inhibit both OVA- and PAF-induced late phase bronchoconstriction and airway hyperreactivity to methacholine in OVA sensitized guinea pigs. PAF administration could also induced dual phase bronchoconstriction in normal guinea pigs. Similarly, late phase airway spasm and airway hyperreactivity after PAF exposure was also blocked by OKY-046. In conclusion, aerosol administration of OKY-046 is a safe and effective way to modulate OVA- and PAF-induced asthmatic reactions. The protective effect of OKY-046 on OVA- and PAF-induced late phase bronchoconstriction and airway hyperreactivity indicates that TXA2 might play an important role in the late phase asthmatic reaction and airway hyperreactivity. The normalization of PAF-induced airway hyperreactivity by OKY-046 also indicates that PAF induced airway inflammation might be through the generation of TXA2.

The inhibitory effect of methotrexate on PAF-induced neutrophil and eosinophil locomotion in asthmatic patients.

We have tested the effect of methotrexate (MTX) on platelet activating factor (PAF)-induced neutrophil and eosinophil locomotion, neutrophil leukotriene B4 (LTB4) generation and mononuclear cell DNA synthesis. Neutrophils from patients treated with low dose methotrexate showed reduced PAF-induced chemotactic responses (727.8 +/- 72.2/10 HPF vs 481.9 +/- 87.3/10 HPF, p < 0.05). Both MTX and the specific PAF antagonist BN-52021 significantly inhibited PAF-induced eosinophil and neutrophil locomotion in a dose-dependent manner. MTX also reduced calcium ionophore-driven LTB4 generation from the neutrophils of asthmatics (358.9 +/- 39.5 pg/10(6) cells vs 240.1 +/- 29.1 pg/10(6) cells, p < 0.05) and attenuated PHA-induced mononuclear DNA synthesis as shown by a reduction in 3H-thymidine uptake and propidium iodide staining. These findings support the view that the beneficial effects of MTX in asthma may be due not only to its anti-mitotic effects on the proliferation of mononuclear cells but also to direct effects on granulocyte locomotion and production of LTB4.

The modulatory effect of immunoglobulin G on the CD23 and HLA-DR expression and cytokine production in different groups of asthmatic patients.

The therapeutic effect and mechanism of action of immunoglobulin G (IgG) on bronchial asthma are not defined. Recently, it has been proposed that mononuclear cell (MNC) infiltration in the airway plays a role in the pathogenesis of asthma. In this study, we evaluated the effect of IgG on the cell receptor expression and cytokine production of MNC from two groups (young atopic and old non-atopic) of stable asthmatic patients. MNCs from both asthmatic patients and normal healthy individuals were obtained after Ficoll-Hypaque separation. Cells were cultured in serum free AIM-V medium, with or without phytohemagglutinin (PHA, 5 micrograms/ml) and IgG (100 micrograms/ml). After culture, MNCs were harvested and stained with monoclonal antibodies for HLA-DR (Ia), CD23 and CD3. MNC supernatants were collected for IL-2 and IL-4 measurement. The results showed an enhancing effect of IgG on young atopic MNC proliferation when stimulated with PHA. The production of IL-2 and IL-4 from MNCs were significantly higher in old non-atopic asthmatics after PHA stimulation. The CD23, but not HLA-DR, expression on CD3 positive T cells and cytokines (IL-2 and IL-4) production were increased by IgG when stimulated with PHA in young atopic asthmatics. To the contrary, the effect of IgG on PHA stimulated MNC proliferation, CD23 and HLA-DR expression on CD23 positive T cells in old non-atopic asthmatics were trivial. Only IL-4 production can be significantly inhibited by IgG. These results suggested that the therapeutic effect of IgG on asthmatics might be variable in different groups of asthmatics.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced eosinophil luminol-dependent chemiluminescence and complement receptor expression by platelet-activating factor and interleukin-5.

The cytokine interleukin-5 (IL-5) and the lipid mediator platelet-activating factor (PAF) have both been shown to be involved in eosinophil differentiation and activation. We have measured and compared the effect of PAF and IL-5 on human eosinophils in terms of their luminol-dependent chemiluminescence (CL) response and their expression of complement receptors, CR1 and CR3. Both IL-5 and PAF enhanced the eosinophil CL response. The optimal concentrations were 40 U/ml for IL-5, and 10(-6) M for PAF. The priming effect of IL-5 was slow and reached a maximal response after 90 minutes incubation. In contrast, the effect of PAF peaked early and declined during incubation. In the complement receptor study, only PAF was able to enhance CR3 expression (p < 0.05) while the effect of IL-5 on eosinophil complement receptor expression was negligible. These results provide evidence that both inflammatory mediator (PAF) and cytokine (IL-5) can activate eosinophils but the effects of IL-5 and PAF on eosinophil CL response appear to be distinct. The activation of eosinophils by PAF and IL-5 may occur through different mechanisms.