These findings are in agreement with previous reports in which increased levels of IL-6 were found in this subset of patients [19]. As FABP-4 has been suggested to be an adipocytokine involved in the cross-talk between adipocytes and macrophages, we investigated whether there was any relationship between FABP-4 serum level and the expression of markers of inflammation and macrophage infiltration

in SAT biopsies obtained from patients with and without lipodystrophy. Up-regulation of CD68 gene expression, a macrophage marker, IDO inhibitor was found in LD+ patients, indicating an inflammatory local environment in SAT. Interestingly, CD68 expression was found to be closely associated with the level of circulating FABP-4 only in LD+ HIV-1-infected patients.

Taken together, these results indicate a more aggressive inflammatory pattern both at the paracrine and at the systemic level in the context of HIV-1-associated lipodystrophy. It is difficult to extrapolate the local data obtained in adipose tissue to the systemic inflammatory profile, but this relationship is particularly relevant in LD+patients. In agreement with previous reports [12], in our HIV-1-infected cohort, FABP-4 was found to be closely associated with lipodystrophy, independently of BMI, sex and age. Although we cannot discount the possibility that exposure to PIs and NRTIs could contribute to the high FABP-4 levels observed in the LD+group, results of previous check details experiments on the effects of PIs and NRTIs indicate that they block adipocyte differentiation. It was found that PIs interfere with adipocyte differentiation whereas NRTIs decrease PPAR-γ expression in adipose tissue. Both PPAR-γ and FABP-4 mRNA expression in adipose tissue increased in both

NRTI-exposed and non-exposed Teicoplanin after rosiglitazone treatment [20]. These observations argue against a direct effect of these treatments on FABP-4 expression via PPAR-γ in HIV-1-infected LD+patients, or at least against an effect with significant systemic repercussions for circulating plasma levels. Consistent with this conclusion, we observed that LD+patients were more frequently treated with PIs and NRTIs than LD− subjects, but FABP-4 levels were similar when the groups were compared according to NRTI and PI treatment (data not shown). In contrast, similar proportions of patients were treated with NNRTIs in the two groups, but in both cases FABP-4 levels were higher in patients treated with NNRTIs than in other patients in the same group. The absence of relationship of any of the antiretroviral drugs with FABP-4 levels in the Coll et al. study also argues against an important effect of cART on FABP-4 levels [12].