Potential Role of IL-18 in the Immunopathogenesis of AIDS, HIVAssociated Lipodystrophy and Related Clinical Conditions

Abstract

IL-18 is a pleiotropic and multifunctional proinflammatory cytokine that is often produced in response to a viral infection. The biological activities of the cytokine are tightly controlled by its natural antagonist, IL-18 binding protein (IL-18BP), as well as by activation of caspase-1, which cleaves the precursor form of IL-18 into its biologically mature form. The cytokine plays an important role in both innate and adaptive antiviral immune responses. Depending upon the context, it can promote TH1, TH2 and TH17 responses. Increased serum concentrations of IL-18 and concomitantly decreased concentrations of its natural antagonist have been described in HIV-infected persons as compared to HIV-seronegative healthy subjects. We discuss in this review article how increased biological activities of IL-18 contribute towards immunopathogenesis of AIDS, HIV-associated lipodystrophy syndrome and related metabolic disturbances. While the advent of potent anti-HIV drugs has significantly enhanced life span of HIV-infected patients, it has also increased the number of these patients suffering from metabolic disorders. The cytokine may prove to be a useful target for therapeutic intervention in these patients.

Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort

“…IL-18 is released upon stimulation of the inflammasome, a multicomponent intracellular protein complex involved in innate immune signaling [13]. Human immunodeficiency virus virions are potent inflammasome triggers in circulating monocytes [14].…”

Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection

“…The cytokine increases HIV replication, attenuates anti-viral innate and adaptive immunity, and contributes towards aberrant immune activation (reviewed in [116,117]). It is noteworthy that certain synonymous mutations in the IL-18 gene promoter that result in increased IL-18 production have been associated with increased susceptibility to the infection in children ( [118]; reviewed in [109]).…”

A new outlook towards kidney injuries

“…NGAL binds with the bacterial siderophore-iron complexes, thus limiting the iron to the bacteria and provides an anti-bacterial activity. Interleukin-18 (IL-18) is a pro-inflammatory cytokine and the role of IL-18 has been well established in the innate immunity based defense against infection (28)(29)(30). IL-18 induces the expression of IFN-γ, which is involved in the Th1-immune response for the elimination of the intracellular pathogens (31,32).…”