Levels of interleukin-18 (IL-18), are elevated in individuals with lipodystrophy - including those with fat loss only or with both fat loss and central fat gain - and “closely linked” to limb fat loss, according to a Danish study which appears in the May 1st issue of Journal of Acquired Immune Deficiency Syndromes.
IL-18 is a cytokine that causes inflammation and tissue destruction. It appears to protect an individual from infectious diseases and tumour growth, but may also contribute to autoimmune disorders. IL-18 also induces tumour necrosis factor (TNF-alpha, associated with HIV-related wasting), and, in turn, TNF-alpha also stimulates IL-18 production.
Previously it has been found that people with advanced HIV infection had elevated levels of IL-18. More recently, HIV-negative individuals who are obese, have type 2 diabetes and/or thickening of the arteries have been found to have elevated levels of IL-18, which decline with weight loss. The Danish researchers set out to discover if IL-18 plays a role in HIV-related lipodystrophy, which shares some of the same features as diabetes, obesity and coronary heart disease.
Forty-two men attending the outpatient clinic of the Department of Infectious Diseases in Copenhagen were assessed by physical exam (later confirmed by DEXA scan to be the correct assessments), and assigned to one of three groups: fat loss only (the lipatrophic group, n=15), fat loss and central fat gain (the mixed group, n=12), and those without lipodystrophy (HIV controls, n=15). There were no men with central fat gain only. Another twelve age-matched HIV-negative men were included in the study as HIV-negative controls. All of the HIV-positive men were on stable and effective HAART; across all three groups, approximately twice as many men were on PI-based HAART as on NNRTI-based HAART, although the men with lipoatrophy had been on HAART significantly longer than the HIV controls (90 vs. 67 months, respectively; p
The main finding of the study was that IL-18 levels were elevated in both the lipoatrophic and mixed groups compared with the HIV controls, and elevated in all HIV-positive men compared with HIV-negative controls. The men with lipoatrophy had the highest levels of IL-18, followed by those with mixed lipodystrophy, and then the HIV controls. However, only the difference between the lipoatrophic group and the HIV controls was found to be statistically significant (345.9 pg/mL vs. 212.6 pg/mL; p
IL-18 levels were not found to be associated with levels of HDL cholesterol, but the HIV-negative controls had statistically significant (p
Although the study was not designed to tease out individual antiretrovirals associated with the development of lipoatrophy, the authors assert that according to unpublished data from the study, the men on d4T had higher levels of IL-18 than the others. Additionally, even those men who had previously been on d4T but switched to other NRTIs did not show a decrease in IL-18 levels (247 vs. 273 pg/mL, before and after d4T switching, respectively).
Since IL-18 was found to be elevated in the men with lipoatrophy and mixed lipodystrophy, the authors suggest that IL-18 is “linked” with fat loss. In support of this, they found that IL-18 levels correlated inversely with limb fat mass (p
The authors suggest that there may well be an association between the inflammation caused by elevated levels of IL-18, and consequently, TNF-alpha, and HAART-induced metabolic changes, “although longitudinal prospective studies are required to fully answer this question.”
Further information on this website
Lipodystrophy - lipodystrophy on aidsmap
Lipodystrophy - overview
Lipodystrophy - factsheets
Lindegaard B et al. High plasma level of interleukin-18 in HIV-infected subjects with lipodystrophy J Acqir Immune Defic Syndr 36 (1), 588-593, 2004.