Background: Insulin resistance and glucose intolerance during ARV treatment seem to depend on increased release of proinflammatory cytokines endowed with anti-insulin activity. We assessed intracellular TNF-a and IFN-g, insulin resistance, metabolic parameters, and anthropometric indexes, in a cohort of ARV-naïve HIV patients before and after starting HAART. Methods: Plasma insulin, glucose, cortisol, triglycerides, cholesterol (total / LDL) levels; HOMA-IR (Homeostasis Model Assessment of Insulin Resistance); body mass index (BMI) and waist-hip ratio (WHR) were evaluated in 18 consecutive HIV+ adults (median age: 33 yrs, range 21-45; 15 male, 3 female; 10 MSM, 3 hetero; 5 ex-IDUs) at baseline and 2, 4, 8, 12, 24, 36 wks after starting ARV treatment including 2 NRTI plus either a NNRTI or a PI. Leukocyte intracellular TNF-a and IFN-g were evaluated at the above times by flow cytometry with monoclonal antibodies (anti-HU TNFα PE and respectively anti-Hu-IFNγFITC, Becton-Dickinson); absolute counts of positive cells/mL were calculated. The significance of variations was assessed by ANOVA for repeated measures and pairwise comparisons (Tukey). Results: Mean baseline CD4 cells (248±220/mL) and HIV RNA (4.82±0.8 log copies/mL) changed respectively to 470±376 and to 0.19±0.5 at end of follow-up. Significant increases compared to baseline were observed for insulin at wk 4 (12.6±7 compared to 8.2±4 mU/L, p=0.05) (Figure 2), total cholesterol at wk 12 (215±43 compared to 170±22 mg/dL, p=0.007) (Figure 4), TNF-a and IFN-g at wk 24 (respectively 4477±3641 compared to 1182±607, and 5243 ± 2035 compared to 1721±619 positive cells/mL, p=0.009 and 0.05) (Figure 5), while baseline glucose (81±7 mg/dL) (Figure 1), triglycerides (120±41mg/dL), and cortisol (11±9mg/dL) (Figure 5) levels did not change significantly. BMI and WHR showed non-significant increases throughout follow-up (Figure 7). HOMA-IR increased from 1,26±0,8 (baseline) to 2,21±1,7 at end of follow-up (p=0,019) (Figure 3). HOMA-IR values showed a significant correlation with number of both TNF-α and IFN-γ - positive cells only after day 60 of follow-up (Figures 8 and 9). Conclusions: In a cohort of ART-naïve patients, normoglycaemic hyperinsulinaemia and moderate insulin resistance without evident body changes are detectable after 4-12 wks of treatment, and seem to be correlated with significant increases of leukocyte cytokine production, (both with TNF-α - and IFN-γ -positive cell number), but not with cortisol levels. No significant differences of bodily shape or anthropometric indexes were detectable at week 36 of follow-up. Further prospective studies are needed in order to correlate the observed metabolic changes with immune response modification
Increase in leukocyte cytokine production correlates with insulin resistance in ART-naive HIV patients after starting antiretroviral treatment
BIGLINO, Alberto;
2004-01-01
Abstract
Background: Insulin resistance and glucose intolerance during ARV treatment seem to depend on increased release of proinflammatory cytokines endowed with anti-insulin activity. We assessed intracellular TNF-a and IFN-g, insulin resistance, metabolic parameters, and anthropometric indexes, in a cohort of ARV-naïve HIV patients before and after starting HAART. Methods: Plasma insulin, glucose, cortisol, triglycerides, cholesterol (total / LDL) levels; HOMA-IR (Homeostasis Model Assessment of Insulin Resistance); body mass index (BMI) and waist-hip ratio (WHR) were evaluated in 18 consecutive HIV+ adults (median age: 33 yrs, range 21-45; 15 male, 3 female; 10 MSM, 3 hetero; 5 ex-IDUs) at baseline and 2, 4, 8, 12, 24, 36 wks after starting ARV treatment including 2 NRTI plus either a NNRTI or a PI. Leukocyte intracellular TNF-a and IFN-g were evaluated at the above times by flow cytometry with monoclonal antibodies (anti-HU TNFα PE and respectively anti-Hu-IFNγFITC, Becton-Dickinson); absolute counts of positive cells/mL were calculated. The significance of variations was assessed by ANOVA for repeated measures and pairwise comparisons (Tukey). Results: Mean baseline CD4 cells (248±220/mL) and HIV RNA (4.82±0.8 log copies/mL) changed respectively to 470±376 and to 0.19±0.5 at end of follow-up. Significant increases compared to baseline were observed for insulin at wk 4 (12.6±7 compared to 8.2±4 mU/L, p=0.05) (Figure 2), total cholesterol at wk 12 (215±43 compared to 170±22 mg/dL, p=0.007) (Figure 4), TNF-a and IFN-g at wk 24 (respectively 4477±3641 compared to 1182±607, and 5243 ± 2035 compared to 1721±619 positive cells/mL, p=0.009 and 0.05) (Figure 5), while baseline glucose (81±7 mg/dL) (Figure 1), triglycerides (120±41mg/dL), and cortisol (11±9mg/dL) (Figure 5) levels did not change significantly. BMI and WHR showed non-significant increases throughout follow-up (Figure 7). HOMA-IR increased from 1,26±0,8 (baseline) to 2,21±1,7 at end of follow-up (p=0,019) (Figure 3). HOMA-IR values showed a significant correlation with number of both TNF-α and IFN-γ - positive cells only after day 60 of follow-up (Figures 8 and 9). Conclusions: In a cohort of ART-naïve patients, normoglycaemic hyperinsulinaemia and moderate insulin resistance without evident body changes are detectable after 4-12 wks of treatment, and seem to be correlated with significant increases of leukocyte cytokine production, (both with TNF-α - and IFN-γ -positive cell number), but not with cortisol levels. No significant differences of bodily shape or anthropometric indexes were detectable at week 36 of follow-up. Further prospective studies are needed in order to correlate the observed metabolic changes with immune response modification
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