IL18
Interleukin-18 precursor (IL-18) (Iboctadekin) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma) [IGIF] [IL1F4]
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The improved effectiveness and safety of the combined antiretroviral therapy (cART) has largely diminished mortality and AIDS-defining morbidity of HIV-patients. Nevertheless, chronic age-related diseases in these individuals are more common and their underlying pathogenic mechanisms of these actions seem to involve accelerated aging and enhanced inflammation. The present study explores markers of these processes in a heterogenous Spanish HIV cohort using peripheral blood samples of HIV-patients and matched uninfected controls. We isolated periheral blood mononuclear cells (PBMCs) and i) compared the expression of a panel of 14 genes related to inflammation and senescence in PBMCs of HIV-patients vs matched uninfected controls, ii) analyzed the expression in HIV-patients in association with a number of demographic, biochemical and immunological parameters and iii) in relation with the current cART they received. PBMCs of HIV-patients displayed significantly increased expression of general inflammatory genes (IL6, IL18 and CXCL10) and this occurs irrespectively of the antiviral therapy they have been receiving. Conversely, levels of senescence-associated genes TP53, SERPINE1andIGFBP3 were slightly but significantly reduced in patients compared to uninfected matched individuals and this effect is related to NNRTI-containing treatments. The expression of the inflammatory markers IL6, IL18, IL1B, TNFA, RELA, CCL2, [[CCL20]] and CXCL10 displayed correlation with certain demographic, morbidity- and HIV infection-related parameters. The levels of TP53 mRNA were positively associated only with plasma LDL. Correlation analysis between the expressions of pairs of genes revealed a different pattern between HIV-patients and controls. The diminished expression of TP53 and SERPINE1 in HIV-patients was also observed at a protein level, and the correlation between the two proteins (p53 and PAI1) in patients and controls showed the opposite trend. In conclusion, HIV-patients show dysregulation of p53 and p53-related mediators, a phenomenon which may be of pathophysiological relevance and could be related to the shorter health- and/or life-span observed in these individuals.
Keywords
- Aging
- Antiretroviral drugs
- HIV
- Inflammation
- NNRTI
- Senescence
- p53
The inflammasomes are innate immune system sensors that control the activation of caspase-1 and induce inflammation in response to infectious microbes and molecules originating from host proteins, leading to the release of pro-inflammatory cytokines, Il1b and IL18, and a particular inflammatory type of cell death termed pyroptosis. It is broadly considered that chronic inflammation may be a common link in age-related diseases, aging being the greatest risk factor for the development of chronic diseases. In this sense, we discuss the role of inflammasomes in non-infectious inflammation and their interest in aging and age-related diseases.
MeSH Terms
- Aging
- Caspase 1
- Humans
- Inflammasomes
- Inflammation
- Interleukin-18
- Interleukin-1beta
- Pyroptosis
Keywords
- Age-related diseases
- Aging
- Chronic inflammatory diseases
- Inflammasomes