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9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV19-21 July 2007, Sydney, Australia |
EFFECT OF ATAZANAVIR AND LOPINAVIR ON RESISTIN EXPRESSION IN PRIMARY HUMAN MACROPHAGES
Antiviral Therapy 2007; 12(Suppl. 2):L26 (abstract no. P-08)
A Bellamine, C Elosua, C Cao and O Flint
Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA
BACKGROUND: Changes in adipokines have been associated with lipodystrophy and increased risk of type 2 diabetes. In particular, a SNP found in the resistin gene is associated with metabolic syndrome in HAART-induced lipodystrophy. We report the effect of atazanavir (ATV) or lopinavir (LPV) with or without ritonavir (ATVr or LPVr) on resistin expression by human primary macrophages.
METHODS: Primary human monocytes from three different donors (M61CC, M27AA and F38CC) were differentiated in vitro into macrophages over 7 days. The cells were then treated with 3, 10 or 30 µM of each of the PIs with or without 2 µM of ritonavir for 24 h. Resistin mRNA expression was determined using RT-PCR and baseline resistin concentrations by ELISA.
RESULTS: Resistin mRNA was reduced by both PIs, but only by LPV in a concentration-dependant fashion. LPV/r inhibited resistin expression more than ATV/r in M61CC and F38CC cells. Similar changes were observed in macrophages treated with ATV or LPV alone. M27AA cells were not affected, except by LPV at 30 µM. M27AA also differed from the other donors in the amount of resistin secreted (67 pg/ml) which was twofold less than F38CC and M61CC (135 and 150 pg/ml, respectively).
| Table 1. (Abstract P-08) | ||||||
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| ATV/r | LPV/r | |||||
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| Donor | 3 µM | 10 µM | 30 µM | 3 µM | 10 µM | 30 µM |
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| M61CC† | 0.7 ±0.1 | 0.9 ±0.1 | 0.8 ±0.1 | 0.7 ±0.0 | 0.4 ±0.0* | 0.1 ±0.0* |
| F38CC† | 0.5 ±0.0* | 0.4 ±0.0* | 0.8 ±0.1 | 0.5 ±0.1* | 0.5 ±0.1* | 0.3 ±0.1* |
| M27AA†,‡ | 1.0 (-0.2–0.3) | 0.6 (-0.1–0.1) | 0.8 (-0.2–0.3) | 0.9 (-0.3–0.5) | 0.7 (-0.2–0.4) | 0.2 (-0.0–0.1) |
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| *Significantly different from the control (P<0.05). †RNA levels are expressed as fold change relative to the control (2 ..Ct). ‡For M27AA results were expressed as fold increase with the range of variation. | ||||||
CONCLUSION: Resistin expression was more affected by LPV than ATV, and there was interindividual variability in the response possibly reflecting variability in the underlying resistin genotypes of the donors and their response to the PIs. Further in vitro and clinical studies will be required to elucidate the mechanisms involved.
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2007-07-24
P-08
Copyright © 2007 - International Medical Press Ltd. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Medical Editor, International Medical Press, 36 St Mary-at-Hill, London EC3R 8DU, United Kingdom.