Energy balance, viral burden, insulin-like growth factor-1, interleukin-6 and growth impairment in children infected with human immunodeficiency virus

Johann-Liang, Rosemary; O'Neill, Loretta; Cervia, Joseph S.; Haller, Ivan; Giunta, Yvonne; Licholai, Teresa; Noel, Gary J.

doi:10.1097/00002030-200004140-00007

Cited by 57 publications

(14 citation statements)

References 27 publications

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“…Markedly decreased levels of circulating IGFBP-3 have been found in patients with systemic JIA [15, 16, 17], Crohn’s disease or cystic fibrosis [18, 19]. Some observations in human diseases suggest a direct relationship between increased IL-6 and reduced IGFBP-3 with chronic overproduction of IL-6 being responsible for the decrease in circulating IGFBP-3: (a) the inverse correlation of intact IGFBP-3 with serum IL-6 levels and with clinical and laboratory parameters of disease activity; (b) the close relation of a rapid fall in IL-6 and C-reactive protein levels with a significant increase in IGFBP-3 levels following elementary diet in Crohn’s disease [18, 20], and (c) the correlation between IL-6 production and decreased levels of IGF-I and IGFBP-3 in HIV-infected children with decreased height velocity [21, 22]. …”

Section: Abnormalities Of the Insulin-like Growth Factor-i System In mentioning

confidence: 99%

Role of Interleukin-6 in Growth Failure: An Animal Model

2002

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Indirect evidence suggests a link between factors produced during the inflammatory response and stunted growth. The demonstration of this link was provided by the observation that mice transgenic for the inflammatory cytokine interleukin-6 (IL-6), expressing high circulating levels of IL-6 since birth, show a marked decrease in growth rate leading to adult mice 50–70% the size of wild-type littermates. The growth defect is completely abolished by neutralization of IL-6. In these mice the production of GH is normal, while circulating levels of IGF-I are markedly decreased. Administration of IL-6 to wild-type mice results in a marked decrease in IGF-I levels. These observations show that in vivo high levels of IL-6 are associated with low levels of IGF-I. However, IL-6 does not directly affect IGF-I production both in vitro and in vivo. In contrast, markedly decreased levels of IGFBP-3 are present in the IL-6 transgenic mice and administration of IL-6 to wild-type mice results in a marked decrease in IGFBP-3 levels. In these mice the decrease in IGFBP-3 levels is associated with impaired formation of the 150 kD ternary complex, even in the presence of normally functional ALS. As a consequence, IL-6 transgenic mice show increased clearance of circulating IGF-I, suggesting that IL-6 decreases IGF-I levels by increased clearance. Proteolytic degradation of IGFBP-3 occurs in the IL-6 transgenic mice, suggesting that the decrease in IGFBP-3 could be at least in part due to proteolysis. The abnormalities of the IGF-I system observed in the IL-6 transgenic mice are similar to those found in patients with systemic juvenile idiopathic arthritis, one of the chronic inflammatory diseases characterized by stunted growth and prominent production of IL-6. The IL-6 transgenic mice represent a faithful animal model of the growth impairment associated with chronic inflammation and may therefore provide information relevant to the understanding and treatment of this complication of inflammatory diseases.

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Section: Abnormalities Of the Insulin-like Growth Factor-i System In mentioning

confidence: 99%

Role of Interleukin-6 in Growth Failure: An Animal Model

2002

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“…There are overlapping effects on growth resulting from a vicious cycle between malnutrition and HIV infection. Malnutrition impairs the immune system and weakens the body’s defences, leading to HIV disease progression ; while HIV infection, related opportunistic infections and chronic inflammation may weaken nutritional status . Repeated episodes of malnutrition during infancy and childhood may have occurred frequently among APH, and lifelong HIV infection can lead to chronic malnutrition and growth retardation as APH age into adulthood.…”

Section: Introductionmentioning

confidence: 99%

Stunting and growth velocity of adolescents with perinatally acquired HIV: differential evolution for males and females. A multiregional analysis from the IeDEA global paediatric collaboration

et al. 2019

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Introduction Stunting is a key issue for adolescents with perinatally acquired HIV (APH) that needs to be better understood. As part of the IeDEA multiregional consortium, we described growth evolution during adolescence for APH on antiretroviral therapy (ART). Methods We included data from sub‐Saharan Africa, the Asia‐Pacific, and the Caribbean, Central and South America regions collected between 2003 and 2016. Adolescents on ART, reporting perinatally acquired infection or entering HIV care before 10 years of age, with at least one height measurement between 10 and 16 years of age, and followed in care until at least 14 years of age were included. Characteristics at ART initiation and at 10 years of age were compared by sex. Correlates of growth defined by height‐for‐age z‐scores (HAZ) between ages 10 and 19 years were studied separately for males and females, using linear mixed models. Results Overall, 8737 APH were included, with 46% from Southern Africa. Median age at ART initiation was 8.1 years (interquartile range (IQR) 6.1 to 9.6), 50% were females, and 41% were stunted (HAZ<−2 SD) at ART initiation. Males and females did not differ by age and stunting at ART initiation, CD4 count over time or retention in care. At 10 years of age, 34% of males were stunted versus 39% of females (p < 0.001). Females had better subsequent growth, resulting in a higher prevalence of stunting for males compared to females by age 15 (48% vs. 25%) and 18 years (31% vs. 15%). In linear mixed models, older age at ART initiation and low CD4 count were associated with poor growth over time (p < 0.001). Those stunted at 10 years of age or at ART initiation had the greatest growth improvement during adolescence. Conclusions Prevalence of stunting is high among APH worldwide. Substantial sex‐based differences in growth evolution during adolescence were observed in this global cohort, which were not explained by differences in age of access to HIV care, degree of immunosuppression or region. Other factors influencing growth differences in APH, such as differences in pubertal development, should be better documented, to guide further research and inform interventions to optimize growth and health outcomes among APH.

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“…In previous experiments, there have been variable inflammatory immune responses to malnutrition. Decreased plasma TNFa production has been reported in rodent models of protein-energy malnutrition (Chan et al 1996, Schaffer et al 1997, Anstead et al 2001, but increased plasma IL6 concentration has been observed in malnourished patients (Malave et al 1998, Johann-Liang et al 2000, de Martino et al 2000. In addition, maternal dietary protein restriction decreased NO synthase (NOS) in endometrium and placenta of pigs during early gestation (Wu et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Unchanged interleukin 6 level of protein and energy restricted goats during late gestation: the role of elevated blood nitric oxide

Tan²,

Sun³

et al. 2012

Journal of Endocrinology

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Twelve pregnant goats were assigned to three dietary treatments during late gestation, namely control (C: metabolizable energy, 5 . 75 MJ/kg; crude protein, 12 . 6% and dry matter basis), 40% protein restricted (PR) and 40% energy restricted (ER), to examine the effects of nutrient restriction on the immune status of pregnant goats. Plasma was sampled on day 90, 125 and 145 from pregnant goats to determine cytokine production (interleukin 2 (IL2), IL6) and tumor necrosis factor a (TNFa)). Peripheral blood mononuclear cells were obtained on day 145 and activated by lipopolysaccharide to determine cytokine production, and then exposed (PR and ER) to sodium nitroprusside (SNP), a nitric oxide (NO) donor, or control to NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), an NO synthase inhibitor to explore the role of NO in regulating cytokine production. Plasma IL2, IL6 and TNFa were not altered during gestation, but NO was increased (P!0 . 05) at gestation day 145 for PR and ER. In vitro, compared with control, NO was lower for PR and ER (P!0 . 001), but IL6 was higher for PR (P!0 . 001) and ER (PZ0 . 11). The addition of SNP decreased IL6 (P!0 . 001, PR; PZ0 . 12, ER) in the malnourished group, and L-NAME increased (P!0 . 001) IL6 in control compared to those treatments without SNP or L-NAME. The results indicate that plasma NO acted as a regulator of cytokine function exhibiting negative feedback to maintain steady plasma IL6 concentration in PR or ER goats during late gestation.

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Energy balance, viral burden, insulin-like growth factor-1, interleukin-6 and growth impairment in children infected with human immunodeficiency virus

Cited by 57 publications

References 27 publications

Role of Interleukin-6 in Growth Failure: An Animal Model

Role of Interleukin-6 in Growth Failure: An Animal Model

Stunting and growth velocity of adolescents with perinatally acquired HIV: differential evolution for males and females. A multiregional analysis from the IeDEA global paediatric collaboration

Unchanged interleukin 6 level of protein and energy restricted goats during late gestation: the role of elevated blood nitric oxide

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