Cytokine Patterns in Adults With Aids

Alonso, Kenneth; Pontiggia, P; Medenica, Rajko; Rizzo, S.

doi:10.1097/00007611-199610001-00299

Cited by 9 publications

(11 citation statements)

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“…Thus, it seems likely that, in vivo, the pathogenesis of biliary cryptosporidiosis is associated not only with the interactions between biliary epithelia and C. parvum, but also with the constellation of systemic dysfunctions after human immunodeficiency virus infection. It is entirely possible that human immunodeficiency virus-induced alterations in local or systemic cytokines, particularly tumor necrosis factor ␣, which has been reported to be increased in patients with AIDS, 27 could increase the susceptibility of biliary epithelia to C. parvum infection and to apoptosis. Recent data with other parasites such as Entamoeba histolytica, Schistosoma mansoni, Trypanosoma cruzi, and Toxoplasma gondii, as well as bacteria in other tissues, are also consistent with the concept that microbial pathogens can kill host cells by an apoptotic mechanism.…”

Section: Discussionmentioning

confidence: 99%

Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism

Chen¹,

Levine²,

Tietz³

et al. 1998

Hepatology

100

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While the clinical features of sclerosing cholangitis secondary to opportunistic infections of the biliary tree in patients with acquired immunodeficiency syndrome (AIDS) are well known, the mechanisms by which microbial pathogens such as Cryptosporidium parvum associated with this syndrome actually cause disease are obscure. We established an in vitro model of biliary cryptosporidiosis employing a human biliary epithelial cell line. Using morphological and biochemical techniques, we examined the interaction of C. parvum with cultured human cholangiocytes. When the apical plasma membrane of polarized, confluent monolayers of human biliary epithelial cells was exposed to C. parvum oocysts that had been excysted in vitro, sporozoites attached to and invaded the cells in a time-, dose-, temperature-, and pH-dependent manner. The infectious process was both plasma membrane domain-and cell-specific, because no attachment or invasion occurred when the basolateral membrane of cholangiocytes was exposed to the parasite, or when a human hepatocyte cell line (HepG2) was used. Time-lapse video microscopy and scanning electron microscopy (SEM) showed that sporozoite attachment was rapid, involved extensive cholangiocyte membrane ruffling, and culminated in parasite penetration into a tight-fitting vacuole formed by invagination of the plasma membrane similar to those found in naturally occurring infection in vivo. Transmission electron microscopy (TEM) showed that C. parvum organisms formed parasitophorus vacuoles and were able to undergo a complete reproductive cycle, forming both asexual and sexual reproductive stages. Unexpectedly, direct cytopathic effects were noted in infected monolayers, with widespread programmed cell death (i.e., apoptosis) of biliary epithelial cells as assessed both morphologically and biochemically beginning within hours after exposure to the organism. The novel finding of specific cytopathic invasion of biliary epithelia by C. parvum may be relevant to the pathogenesis and possible therapy of the secondary sclerosing cholangitis seen in AIDS patients with biliary cryptosporidiosis. (HEPATOLOGY 1998;28:906-913.)

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Section: Discussionmentioning

confidence: 99%

Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism

Chen¹,

Levine²,

Tietz³

et al. 1998

Hepatology

100

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“…This therapy is called highly-active antiretroviral therapy (HAART), which continuously suppresses viral replication and restores the function of the immune system in HIV-1-infected patients. 1 AIDS Medical Center, Osaka National Hospital, National Hospital Organization, Osaka City, Osaka, Japan. Many studies have been conducted on the importance of cytokines in the pathogenesis of HIV-1 infection because it affects the immune system (11).…”

Section: Introductionmentioning

confidence: 99%

“…Many studies have been conducted on the importance of cytokines in the pathogenesis of HIV-1 infection because it affects the immune system (11). In the pre-HAART era, the expression levels of various cytokines reportedly increased, along with the progression of immunodeficiency (1,3). Since in previous studies researchers have reported that a Th-1/Th-2 imbalance is strongly involved in HIV pathogenesis (5,7), the cytokines responsible for the Th-1/Th-2 balance, such as IL-2 (18), IL-6 (4), IL-10 (2), and IFN-g, have been studied in detail (1).…”

Section: Introductionmentioning

confidence: 99%

“…In the pre-HAART era, the expression levels of various cytokines reportedly increased, along with the progression of immunodeficiency (1,3). Since in previous studies researchers have reported that a Th-1/Th-2 imbalance is strongly involved in HIV pathogenesis (5,7), the cytokines responsible for the Th-1/Th-2 balance, such as IL-2 (18), IL-6 (4), IL-10 (2), and IFN-g, have been studied in detail (1). On the other hand, in the post-HAART era, the increased cytokine expression was decreased by ART (14,16,22,23,25).…”

Section: Introductionmentioning

confidence: 99%

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Sustained High Levels of Serum Interferon-γ During HIV-1 Infection: A Specific Trend Different from Other Cytokines

et al. 2010

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The expression levels of various cytokines increase with the progression of HIV-1 infection. However, the effects of antiretroviral therapy (ART) on serum cytokine levels have not been fully determined. In this study we measured serum cytokine levels of 35 HIV-1-infected Japanese adults. We first performed a cross-sectional study and observed that TNF-α, IL-6, IL-10, IL-18, and IL-7 levels all showed significant increases in those with advanced disease, and that this had a significant negative correlation with the CD4 cell count. However, IFN-γ levels did not show this relationship. A longitudinal study in 18 HIV-1-infected patients with a CD4 cell count <350/μL revealed that the introduction of ART reduced cytokine levels. Significant reductions of IL-7, IL-10, IFN-γ, and IL-18 levels were observed on days 30, 60, 90, and 90 after the initiation of ART, respectively. These results indicate a discrepancy between cross-sectional and longitudinal studies of serum levels of IFN-γ. To clarify this, we investigated serum IFN-γ levels in each patient. In 5 of the 15 patients IFN-γ levels did not decrease, even after ART initiation, and remained at 5 pg/mL or higher on day 120 after ART initiation. Higher IFN-γ levels (>5 pg/mL) were also observed in 2 of 7 asymptomatic patients, and 2 of 11 patients who underwent ART for 1 year or longer. These data demonstrate that IFN-γ levels in some patients increased and remained high even after the initiation of ART, which was a specific observation different from those of the other cytokines.

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“…The progression of HIV infection is commonly associated with a general activation of the immune system, which is reflected by elevated plasma levels of several cytokines and immune-activation molecules [29][30][31][32][33]. The higher rates of lymphocyte protein synthesis in AIDS patients might therefore be the result of this generalized activation of the immune system.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte protein synthesis is increased with the progression of HIV-associated disease to AIDS

CASO¹,

Garlick²,

Gelato³

et al. 2001

Clinical Science

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HIV infection has been shown to affect lymphocyte function and to reduce lymphocyte responsiveness in vitro to mitogenic stimulation, but little is known about lymphocyte metabolism in vivo and how it is affected during the course of the disease. This study investigated the metabolic activity of lymphocytes in vivo through the progression of HIV-associated disease. Lymphocyte protein synthesis was measured with L-[(2)H(5)]phenylalanine (45 mg/kg body weight) in healthy volunteers (n=7), in patients who were HIV-positive (n=7) but asymptomatic, and in patients with AIDS (n=8). The rates of lymphocyte protein synthesis [expressed as a percentage of lymphocyte protein, i.e. fractional synthesis rate (FSR)] were not altered in HIV-positive patients compared with healthy controls (7.9+/-1.28% and 9.1+/-0.53%/day respectively), but were significantly elevated in AIDS patients (14.0+/-1.16%/day; P<0.05). The serum concentration of the cytokine tumour necrosis factor-alpha (TNF-alpha) increased with the progression of the disease, and TNF-alpha levels were significantly higher in AIDS patients (6.81+/-0.88 ng/l) than in healthy controls (3.09+/-0.27 ng/l; P<0.05). Lymphocyte protein FSR was positively correlated with serum TNF-alpha concentration (r=0.55, P=0.009) and negatively correlated with CD4(+) lymphocyte count (r=-0.70, P=0.004). The elevation of lymphocyte protein synthesis in AIDS patients suggests a higher rate of turnover of lymphocytes. This may be associated with a generalized activation of the immune system, which is also reflected by the elevated serum TNF-alpha concentration in the late stages of HIV-associated disease.

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Cytokine Patterns in Adults With Aids

Cited by 9 publications

References 0 publications

Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism

Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism

Sustained High Levels of Serum Interferon-γ During HIV-1 Infection: A Specific Trend Different from Other Cytokines

Lymphocyte protein synthesis is increased with the progression of HIV-associated disease to AIDS

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