Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine essential for defense against intracellular pathogens is often elevated in the plasma of patients with HIV infection. The increased production of TNF-alpha in late stages of HIV disease has been postulated to be an important factor in disease progression by causing increased HIV relication. Concentrations of soluble TNF Type II receptors are predictors of disease progression and death, suggesting that TNF alpha production is of clinical significance. We postulate that diseases associated with chronic elevations in TNF-alpha production such as rheumatoid arthritis and AIDS may be more responsive to blockade of TNF receptors than acute diseases such as septic shock. Since IL-6 activity is inducible through induction of TNF and since IL-2 administration increases both plasma levels of TNF and IL-6, we propose to test the activity of TNFR:Fc on IL-2 induced, presumably TNF-dependent, IL-6 levels that are increased during infusion of rh IL-2. ACTG 928, a nested substudy of ACTG 328, is designed as a test of concept to determine whether soluble TNF receptor can diminish IL-6 levels and/or TNF bioactivity in subjects with HIV infection who are receiving IL-2. The results of this prospective substudy will provide important information regarding cytokine regulation and toxicities during infusions of IL-2 that may permit the design of simple, more readily tolerated IL-2 regimens for widespread administration and potentially provide preliminary data to support pursuing TNFR:Fc as an adjunctive anti-HIV therapy.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000080-39
Application #
6441884
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2000-12-01
Project End
2001-11-30
Budget Start
Budget End
Support Year
39
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Randis, Tara M; Rice, Madeline Murguia; Myatt, Leslie et al. (2018) Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis. J Perinat Med 46:926-933
Clark, Erin A S; Weiner, Steven J; Rouse, Dwight J et al. (2018) Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth. Am J Perinatol 35:1012-1022
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Saade, G R; Thom, E A; Grobman, W A et al. (2018) Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm. Ultrasound Obstet Gynecol 52:757-762
Inker, Lesley A; Grams, Morgan E; Levey, Andrew S et al. (2018) Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium. Am J Kidney Dis :
Juraschek, Stephen P; Miller 3rd, Edgar R; Appel, Lawrence J (2018) Orthostatic Hypotension and Symptoms in the AASK Trial. Am J Hypertens 31:665-671
Juraschek, Stephen P; Appel, Lawrence J; Miller 3rd, Edgar R (2017) Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension. Am J Hypertens 30:871-875
O'Toole, John F; Bruggeman, Leslie A; Madhavan, Sethu et al. (2017) The Cell Biology of APOL1. Semin Nephrol 37:538-545
Chen, Teresa K; Tin, Adrienne; Peralta, Carmen A et al. (2017) APOL1 Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks with Hypertension-Attributed CKD. Clin J Am Soc Nephrol 12:1771-1777
Catalano, Patrick M; Shankar, Kartik (2017) Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ 356:j1

Showing the most recent 10 out of 753 publications