Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals

Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals

AtriplaR/anti-TB combination in TB/HIV patients. Drug in focus

Co-administration of anti-tuberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and several antiretroviral drugs is complicated by pharmacokinetic drug-drug interaction. Pubmed and Google search following the key words tuberculosis, HIV, emtricitabine, tenofovir efavirenz, interaction were used to find relevant information on each drug of the fixed dose combination AtriplaR RESULTS: Information on generic name, trade name, pharmacokinetic parameter, metabolism and the pharmacokinetic interaction with Anti-TB drugs of emtricitabine, tenofovir, and efavirenz was obtained. Fixed dose combination of emtricitabine/tenofovir/efavirenz (ATRIPLAR) which has been approved by Food and Drug Administration shows promising results as far as safety and efficacy is concerned in TB/HIV co-infection patients, hence can be considered effective and safe antiretroviral drug in TB/HIV management for adult and children above 3 years of age

Should adrenaline be used in patients with hemodynamically stable anaphylaxis? Incident case control study nested within a retrospective cohort study

Although adrenaline (epinephrine) is a cornerstone of initial anaphylaxis treatment, it is not often used. We sought to assess whether use of adrenaline in hemodynamically stable patients with anaphylaxis could prevent the development of hypotension. We conducted a retrospective cohort study of 761 adult patients with anaphylaxis presenting to the emergency department (ED) of a tertiary care hospital over a 10-year period. We divided the patients into two groups according to the occurrence of hypotension and compared demographic characteristics, clinical features, treatments and outcomes. Of the 340 patients with anaphylaxis who were normotensive at first presentation, 40 patients experienced hypotension during their ED stay. The ED stay of the hypotension group was significantly longer than that of patients who did not experience hypotension (496 min vs 253 min, P = 0.000). Adrenaline use in hemodynamically stable anaphylaxis patient was independently associated with a lower risk of developing in-hospital occurrence of hypotension: OR, 0.254 [95% CI, 0.091-0.706]. Adrenaline use in hemodynamically stable anaphylaxis patients was associated with a reduced risk of developing in-hospital occurrence of hypotension. Adverse events induced by adrenaline were rare when the intramuscular route was used

Cisplatin-based chemotherapy changes the incidence of bilateral testicular cancer

Background: The introduction of cisplatin-based chemotherapy has remarkably increased the survival of testicular cancer patients. With this success, the concern for a contraIateral testicular tumor has increased. The aim of this study was to investigate whether the risk for contralateral testicular tumor development was influenced by cisplatin-based chemotherapy, Methods: The incidence of a contralateraI testicular tumor among 365 consecutive patients with a nonseminoma testicular tumor, diagnosed in the period 1980 and 1995, was established and related to previous therapy. Results: Eleven of 365 men (3%) developed a contralateral testicular tumor, After a total of 2403 person-pears at risk, 4 of 225 chemotherapy-treated patients (1.8%) developed a contralateraI testicular tumor, and 7 of 140 patients (5%) treated with orchidectomy alone developed a contralateraI tumor. In comparison to this surveillance subgroup, patients previously treated with chemotherapy have a relative risk of 0.30 to develop a second testicular tumor. Conclusions: In Dutch men with a nonseminoma testicular tumor, the incidence of a contralateral testicular tumor is 3%, which is 60-fold the expected incidence rate of testicular cancer, A three times lower incidence rate of a contralateral testicular tumor was found in the chemotherapy subgroup compared with those on surveillance. This supports the hypothesis that cisplatin-based chemotherapy may eradicate carcinoma in situ or early testicular cancer