3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 23-26 October 2001, Athens, Greece

ELEVATED IN VITRO TUMOUR NECROSIS FACTOR A RELEASE FROM ABDOMINAL SUBCUTANEOUS ADIPOSE TISSUE IN HIV-INFECTED SUBJECTS WITH LIPODYSTROPHY

Antiviral Therapy 2001; 6(Suppl. 4):16 (abstract no. 22)

JA Johnson, JB Albu, Q He, ES Engelson and DP Kotler
St Luke's-Roosevelt Hospital Center, Columbia University, New York, NY, USA

BACKGROUND: The aetiology of HIV-associated lipodystrophy (HIVL) is multifactorial. Persistent proinflammatory activity, as a consequence of immune reconstitution, might potentiate fat redistribution.

OBJECTIVE: We compared the secretion of tumour necrosis factor (TNFα), leptin, glycerol, and lactate from subcutaneous adipose tissue (SAT) during short term in vitro incubation of SAT in HIVL-positive, HIV without lipodystrophy and controls.

METHODS: SAT was aspirated from 10 healthy volunteers, 18 HIVL-positive, and 12 HIVL-negative subjects. Nine HIV subjects also had aspirates from buffalo humps. Twenty-one of 30 HIV-positive subjects were currently taking antiretroviral agents, including nucleosides (NRTI) in 24, protease inhibitors (PI) in 17, and non-nucleosides (NNRTI) in nine. Short-term (3 h) cultures of tissue expfants were performed, and the release of TNFα, leptin, lactate and glycerol into the medium were measured. TNFα and lactate data were log transformed to approximate a normal distribution. Body fat compartments in 32 subjects were quantified by whole-body MRI.

RESULTS: HIVL-positive had more visceral fat (P<0.01) and SAT(P=0.01) than HIVL-negative. Log TNFα release from SAT was higher in HIVL-positive than in HIVL-negative or control (both P<0.01, oneway ANOVA). Log TNFα release was not related to use of antiviral therapy (P=O.3).Log lactate release was higher in HIVL-positive (P<0.04) and HIVL-negative (P=0.06)than in controls, but similar in HIVL-positive and HIVL-negative. Log lactate release was associated with NRTI (P=0.05), but not PI or NNRTI therapy. HIVL-negative also had higher glycerol release than controls (P=0.04). Leptin release was similar in all three groups (P=0.9).The release of log TNF (P=0.03), log lactate (P=0.02), glycerol (P=0.07), and lept in (P=0.03) were higher in SAT than in buffalo hump (n=9, paired t-test). There were no significant associations between log TNFα or lactate release and SAT or VATin the HIV-infected subjects.

CONCLUSIONS: (1) TNFα release from SAT is elevated in HIVL-positive subjects; (2) TNFα release is higher in SAT than in buffalo hump; (3) lactate and glycerol release from SAT are elevated in HIV-positive subjects, implying higher basal lipolysis; and (4) elevated lactate release from SAT is associated with NRTI therapy.

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