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. Design: 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 (> 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-ª, interleukin (IL)-2, IL-4, IL10, IL-12, tumor necrosis factor-Æ (TNF-Æ)] 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 ¼ 0.0001), and TNF-Æ (P ¼ 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. ATApositive women also showed a better response to tetanus toxoid (P ¼ 0.021) and a lower median fluorescence intensity of CD14/DR (P ¼ 0.033). Plasma C-peptide values were higher in ATA-positive women compared with ATA-negative women (P ¼ 0.033), even if in the normal range (, 4 ng/ml) in all but one of the ATA-positive patients. Conclusion: 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-Æ 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