Correlation of adipocytokine levels in different types of lipodistrophy in HIV/AIDS patients

[D. M. Cvetković]

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medicina - klinička farmakologija / medicine - clinical pharmacology

Primenom kombinovane antiretrovirusne terapije (combination antiretroviral therapy, cART) došlo je do značajnog smanjenja morbiditeta i mortaliteta kod osoba inficiranih virusom humane imunodeficijencije (Human Immunodeficiency Virus, HIV) i sindromom stečene imunodeficijencije (Acquired immune deficiency syndrome, AIDS). Sa produženjem životnog veka pacijenata sa HIV-om od značaja je postalo praćenje neželjenih efekata cART-a među kojima se posebno izdvajaju poremećaj metabolizma lipida, dislipidemija, kao i periferna lipoatrofija i visceralna lipohipertrofija, zajednički označene kao lipodistrofija, i insulinska rezistencija. Sindrom lipodistrofije obuhvata tri klinička stanja koja se karakterišu poremećenom distribucijom telesnih masti, a to su lipoatrofija (gubitak potkožnog masnog tkiva), lipohipertrofija (povećanje visceralnog masnog tkiva) i mešoviti tip koji predstavlja kombinaciju dva navedena stanja. Skorašnja istraživanja su pokazala kompleksnu ulogu masnog tkiva, koje predstavlja metabolički aktivan endokrini organ i koje oslobađa u cirkulaciju biološki aktivne peptide, odnosno adipocitokine. Ćelije masnog tkiva aktivno proizvode brojne predstavnike familije citokina, kao što su adiponektin, leptin, rezistin, faktor tumorske nekroze alfa (TNF–α), inhibitor aktivatora plazminogena (PAI-1) i razne druge interleukine (IL). Adipocitokini imaju različite uloge u imunom odgovoru (interleukini), inflamaciji (IL-1β, IL-6, IL-8, IL-10, monocitni hemotaksni protein-1 (MCP- 1)), metabolizmu glukoze (leptin, adiponektin, rezistin), osetljivosti na insulin (leptin, adiponektin), ćelijskoj adheziji (PAI-1), rastu i funkciji vaskularnih ćelija (faktor rasta vaskularnog endotela, VEGF), razvoju ateroskleroze, adipogeneze i drugih bioloških procesa. U ovom radu je ispitivana povezanost nivoa adipocitokina i različitih podtipova lipodistrofije kod bolesnika sa HIV infekcijom. Ciljevi: (I) Utvrditi učestalost lipodistrofije kao i podtipova lipodistrofije (lipoatrofija, lipohipertrofija, mešoviti tip lipodistrofije) kod bolesnika sa HIV/AIDS-om; (II) Ispititati povezanost dužine trajanja cART-a i broja cART kombinacija sa pojavom lipodistrofije (odnosno odgovarajućeg podtipa lipodistrofije); (III) Ispititati povezanost nivoa adipocitokina (adiponektin, rezistin, leptin, interleukini (IL-2, IL-4, IL-6, IL-8, IL-10; IL-1 α, IL-1β), TNF- α, PAI-1, MCP-1, VEGF, EGF, IFN-γ, cistatin C) kod bolesnika sa HIV/AIDS-om sa i bez 2 lipodistrofije; (IV) Ispititati povezanost nivoa adipocitokina (adiponektin, rezistin, leptin, interleukini (IL-2, IL-4, IL-6, IL-8, IL-10; IL-1 α, IL-1β), TNF-α, PAI-1, MCP-1, VEGF, EGF, IFN-γ, cistatin C)) kod bolesnika sa HIV/AIDS-om sa različitim podtipovima lipodistrofije...

The introduction of combination antiretroviral therapy (cART) has led to a significant decrease in morbidity and mortality in people infected with Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). With the prolongation of the life span of patients with HIV, it became increasingly important to monitor adverse effects associated with cART, such as lipid metabolism disorders, dyslipidemia, and peripheral lipoatrophy and visceral lipohypertrophy, commonly referred to as lipodystrophy, and insulin resistance. Lipodystrophy syndrome (LD) groups together three clinical conditions characterized by fat redistribution: lipoatrophy (LA, loss of subcutaneous adipose tissue), lipohipertrophy (LH, increase in visceral adipose tissue), and a mixed lipodystrophy type (MFR, mixed fat redistibution) that represents a combination of the two states mentioned above. A number of evidence have demonstrated a much more complex function of adipose tissue, which is now considered not only an energy storage organ but also a metabolically active endocrine organ that releases bioactive peptides (e.g., adipokines) into the blood stream. Fat cells actively secrete many members of the cytokine family, such as adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-α), plasminogen activator inhibitor (PAI-1) and various interleukins (IL). Adipokines have been proposed to play specific roles in immune response (interleukins), inflammation (IL-1β, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1)), glucose metabolism (leptin, adiponectin), insulin sensitivity (leptin, adiponectin), cell adhesion (PAI-1), vascular growth and function (vascular endothelial growth factor, VEGF), development of atherosclerosis, adipogenesis and other biological processes. In our research, we investigated the association between levels of adipocytokines and different lipodystrophy subtypes in HIV/AIDS patients. Aims: (I) to assess the prevalence of lipodystrophy and its subtypes (lipoatrophy, lipohypertrophy, mixed fat redistribution) in HIV/AIDS patients; (II) to examine the relationship between the duration of cART and the number of cART combinations with the prevalence of lipodystrophy (as well as with different lipodystrophy subtypes); (III) to determine the correlation between adipocytokine levels (adiponectin, resistin, leptin, interleukins (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1 α, IL-1β), PAI-1, MCP-1, VEGF, EGF, IFN6 γ, cystatin C) in HIV/AIDS patients with or without lipodystrophy; (IV) to determine the correlation between adipocytokine levels (adiponectin, resistin, leptin, interleukins (IL-2, IL- 4, IL-6, IL-8, IL-10, IL-1 α, IL-1β), PAI-1, MCP-1, VEGF, EGF, IFN-γ, cystatin C) in HIV/AIDS patients with different subtypes of lipodystrophy...

HIV, lipodistrofija, adipocitokini

HIV, lipodystrophy, adipocytokines

616.988:615.2(043.3)

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