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Anti-Inflammatory Interleukin 10 Inversely Relates to Coronary Atherosclerosis in Persons With Human Immunodeficiency Virus.

ABSTRACT: Interleukin 10 (IL-10) is an anti-inflammatory cytokine that may be protective against coronary atherosclerosis. In an observational study of persons with human immunodeficiency virus (PWH) and uninfected controls, IL-10 was measured in serum samples by means of enzyme-linked immunosorbent assay, and coronary atherosclerosis was assessed using computed tomographic angiography. Among PWH, a 10-fold decrease in IL-10 was associated with a 2.6-fold increase in the odds of coronary plaque (P = .01), after controlling for traditional and nontraditional cardiovascular risk factors. IL-10 was also inversely associated with total coronary plaque (? = -0.19; P = .02) and noncalcified coronary plaque (? = -0.24; P = .004). Our findings suggest a role for IL-10 in mitigating atherosclerosis in PWH. Clinical Trials Registration. NCT00455793.

SUBMITTER: Fourman LT

PROVIDER: S-EPMC7325621 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Anti-Inflammatory Interleukin 10 Inversely Relates to Coronary Atherosclerosis in Persons With Human Immunodeficiency Virus.

Fourman Lindsay T LT Saylor Charles F CF Cheru Lediya L Fitch Kathleen K Looby Sara S Keller Kiana K Robinson Jake A JA Hoffmann Udo U Lu Michael T MT Burdo Tricia T Lo Janet J

The Journal of infectious diseases 20200201 4

Interleukin 10 (IL-10) is an anti-inflammatory cytokine that may be protective against coronary atherosclerosis. In an observational study of persons with human immunodeficiency virus (PWH) and uninfected controls, IL-10 was measured in serum samples by means of enzyme-linked immunosorbent assay, and coronary atherosclerosis was assessed using computed tomographic angiography. Among PWH, a 10-fold decrease in IL-10 was associated with a 2.6-fold increase in the odds of coronary plaque (P = .01), ...[more]

PMID: 31077265

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Project description:Epstein Barr virus (EBV) is a gamma herpes virus associated with certain malignancies and autoimmune diseases. EBV maintains latency in B cells with occasional reactivation, in part by overcoming the host immune response with viral homologs of several human proteins. EBV interleukin 10 (vIL-10), a lytic phase protein, is a homolog of human IL-10 (hIL-10). The effect of vIL-10 on human monocytes, which are one of the first immune cells to respond to infection, is not known. To understand the role of vIL-10, monocytes from peripheral blood mononuclear cells were stimulated with hIL-10 or vIL-10. Human IL-10 stimulated STAT3 phosphorylation, which is required for suppression of inflammatory responses. However, vIL-10 induced significantly lower phosphorylation of STAT3 compared to hIL-10, and was less efficient in downregulating inflammatory genes. vIL-10 significantly reduced the expression of scavenger receptor CD163 on monocytes, suggesting inhibition of M2 polarization. Furthermore, uptake of apoptotic cells was reduced in vIL-10-stimulated monocytes compared to hIL-10-stimulated monocytes. A neutralizing antibody to IL-10R1 inhibited STAT3 phosphorylation induced by either hIL-10 or vIL-10, suggesting that vIL-10 signals through IL-10R1. Interestingly, vIL-10 suppressed hIL-10-induced STAT3 phosphorylation and inhibited upregulation of suppressors of inflammatory response by hIL-10. We further show that vIL-10 levels were significantly higher in plasma samples from systemic lupus erythematosus (SLE) patients compared to matched unaffected controls. vIL-10 levels did not correlate with hIL-10 levels, but were associated with levels of IgA antibodies to EBV viral capsid antigen, which is an indirect measure of viral reactivation. We propose that the suppression of hIL-10- induced anti-inflammatory genes by vIL-10, together with an increase in inflammatory gene expression, may overcome the anti-inflammatory effects of hIL-10 and exacerbate autoimmune responses in systemic autoimmune diseases.

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Anti-Inflammatory Interleukin 10 Inversely Relates to Coronary Atherosclerosis in Persons With Human Immunodeficiency Virus.

Publications

Anti-Inflammatory Interleukin 10 Inversely Relates to Coronary Atherosclerosis in Persons With Human Immunodeficiency Virus.

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