Cytokine production in women with antiretroviral treatment-associated breast fat accumulation and limb wasting.
OBJECTIVE
To test the cytokine production of peripheral blood mononuclear cells in a group of HIV-infected women with breast enlargement and lower limb wasting while receiving antiretroviral therapy (ART) including a protease inhibitor.


METHODS
Case-control study including 20 women with fat tissue alterations and 20 matched controls treated with comparable ART.


METHODS
Adipose tissue alterations (ATA) were defined by increased breast size (> or = 2 bra sizes) accompanied by lower limb fat wasting. A randomly selected subset of patients underwent analyses including: dual energy X-ray absorptiometry, metabolic and endocrine assays, in vitro cytokine production testing [interferon-gamma, interleukin (IL)-2, IL-4, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha)] after appropriate stimulation; T-cell phenotyping, T-helper function after stimulation with either tetanus toxoid, influenza antigen, allogeneic peripheral blood lymphocytes, and phytohemagglutinin. Endocrinological study included the determination of plasma concentrations of prolactin, growth hormone, testosterone, adrenocorticotropic hormone, cortisol and C-peptide.


RESULTS
In vitro production of IL-12 was higher (P = 0.0001), and TNF-alpha (P = 0.0093) and IL-10 (P < 0.0001) production were lower in stimulated peripheral blood mononuclear cells of ATA-positive women compared with ATA-negative women. ATA-positive women also showed a better response to tetanus toxoid (P = 0.021) and a lower median fluorescence intensity of CD14/DR (P=0.033). Plasma C-peptide values were higher in ATA-positive women compared with ATA-negative women (P = 0.033), even if in the normal range (< 4 ng/ml) in all but one of the ATA-positive patients.


CONCLUSIONS
HIV-1-infected women who developed breast enlargement and lower limb fat wasting while receiving ART had a favorable immunological profile with efficient IL-12 production and T-helper function, and with TNF-a production in the range of a HIV-negative reference population. These findings suggest that the rescue of some immune functions under ART may be involved in the pathogenesis of this particular adipose tissue disorder.
Galli
Massimo
M
Institute of Infectious and Tropical Diseases, University of Milan, Sacco Hospital, Milan, Italy. masgalli@mailserver.unimi.it
Gervasoni
Cristina
C
Ridolfo
Anna Lisa
AL
Trabattoni
Daria
D
Santambrogio
Sara
S
Vaccarezza
Mauro
M
Meroni
Luca
L
Trifirò
Giuliana
G
Moroni
Mauro
M
Norbiato
Guido
G
Clerici
Mario
M
D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015992:Body Mass Index; D001940:Breast / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D019247:HIV Wasting Syndrome / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines