Increased serum interferon alpha in HIV-1 associated lipodystrophy syndrome.
BACKGROUND
A syndrome of lipodystrophy (LD) associated with peripheral lipoatrophy and central/visceral adiposity has been reported in HIV-1-infected patients treated by combined antiretroviral therapy (ART). Lipid metabolism is partly regulated by both steroid hormones and cytokines and we have previously reported that dyslipidaemia in LD-positive men is correlated to an increase in cortisol : DHEA ratio (Christeff et al., AIDS 1999;13:2251). In this study we questioned whether it is also related to cytokine perturbations.


METHODS
A cross-sectional study was performed on 42 HIV-1-positive men on ART, 27 of whom had symptoms of LD, defined by computed tomography scan. Serum cytokines (IFN-alpha, TNF-alpha, sTNF-RI, sTNF-RII, IL-6, IL-1beta and IL-2) and lipids [cholesterol, triglycerides (TG) and their subclasses], and apolipoproteins (Apo), were determined.


RESULTS
Serum IFN-alpha was markedly increased in LD-positive compared with LD-negative men and controls. IL-6 and TNF-alpha concentrations were also significantly elevated in HIV-positive men compared to controls but the levels of these cytokines did not differ between the two groups of patients. A significant positive correlation was found between accumulation of IFN-alpha and increased levels of cholesterol, TG, VLDL cholesterol, VLDL TG, ApoB and ApoB-ApoA1 ratio. A multivariate forward-performed analysis revealed that IFN-alpha is the best marker for lipid perturbations associated to LD, followed by insulin and cortisol : DHEA ratio.


CONCLUSIONS
This study demonstrates an association between serum IFN-alpha and lipid alterations in LD-positive men. The concomittant action of IFN-alpha and cortisol : DHEA ratio is probably one of the mechanisms responsible for hyperlipidaemia in LD syndrome.
Christeff
N
N
Institut Pasteur, Paris, France.
Melchior
J-C
JC
de Truchis
P
P
Perronne
C
C
Gougeon
M-L
ML
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D003430:Cross-Sectional Studies; D003687:Dehydroepiandrosterone / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006949:Hyperlipidemias / Q000097:blood / Q000821:virology; D016898:Interferon-alpha / Q000097:blood*; D007375:Interleukin-1 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008060:Lipodystrophy / Q000097:blood* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016898:Interferon-alpha; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003687:Dehydroepiandrosterone; D006854:Hydrocortisone