TNF and AIDS: Two sides of the same coin?

Pallarés-Trujillo, J.; Fj, López-Soriano; Jm, Argilés

doi:10.1002/med.2610150605

Cited by 8 publications

(5 citation statements)

References 102 publications

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“…Those individuals with the most severe illness were on average slightly older than the control group (42 Ϯ 1.5, range 35-45 vs. 34 Ϯ 2.5, range [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. The HIV and AIDS with weight-loss groups had the smallest body mass indices (BMI, wt/h 2 ); but in the HIV group this was the result of the higher proportion of females in this group rather than the wasting seen in the AIDS with weight loss group.…”

Section: Resultsmentioning

confidence: 99%

Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.

et al. 1997

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Section: Resultsmentioning

confidence: 99%

Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.

et al. 1997

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“…It has been suggested that TNF-α might have an important role in the pathogenesis and progression of HIV-associated disease [37,38]. TNF-α is one of the cytokines that is produced by monocytes and macrophages in response to the HIV virus [39,40], but it has also been shown to enhance HIV replication in infected cells [41][42][43] and to be positively correlated with circulating HIV RNA levels in HIV-positive patients [32].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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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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“…The results of intensive research have lead to the suggestion that HIV replication is dependent on the activation of the nuclear factor kappa B (NF-B), which is a transcriptional factor normally implicated in lymphocyte activation by cytokines. 142 NF-B is a cytosolic protein heterodimer, composed of 50 kDa and 65 kDa subunits, normally suppressed through their binding to inhibitory proteins (I-B). Activation of NF-B involves dissociation from the I-B proteins.…”

Section: Ubiquitin and Aidsmentioning

confidence: 99%

“…The ceramide which is formed is somehow involved in the activation of NF-B by release of the I-B protein. 142 Very interestingly, Palombella et al 143 have recently described that the ubiquitin-proteasome pathway is required for processing the NF-B, (50kDa) subunit of the heterodimeric complex and degrades the I-B proteins, thus ubiquitin could have a pivotal role in the activation of NF-B. In addition, we have previously demonstrated that TNF is able to activate the ubiquitin dependent pathway, 139,140 so that it may be suggested that TNF-dependent NF-B activation could well involve the ubiquitin system.…”

Section: Ubiquitin and Aidsmentioning

confidence: 99%

“…In fact, this last cytokine has been associated with some of the characteristic metabolic abnormalities of the AIDS patients such as hyperlipidemia. 142 Very interestingly, Loeb and Haas 144 have reported that alpha-interferon can induce the production of an ubiquitin cross-reactive protein (UCRP) which seems to be a protein serving as a trans-acting binding factor directing the association of ligated target proteins to intermediate cytoskeletal filaments.…”

Section: Ubiquitin and Aidsmentioning

confidence: 99%

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