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

Samarani, Suzanne; Allam, Ossama; Sagala, Patrick; Aldabah, Zainab; Jenabian, Mohammad Ali; Mehraj, Vikram; Tremblay, Cécile; Routy, Jean Pierre; Amre, Devendra; Ahmad, Ali

doi:10.1016/j.cyto.2016.01.006

Cited by 29 publications

(32 citation statements)

References 133 publications

(168 reference statements)

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“…Here, we demonstrated that a CCR1 antagonist decreased the protein level of IL‐1 β and enhanced the level of IL‐1RA in the DRG, which is crucial for impaired nociceptive transmission under neuropathic pain conditions. IL‐18 also belongs to the IL‐1 superfamily . The pronociceptive actions of IL‐18 are under the control of its naturally occurring antagonist IL‐18BP, which can be produced constitutively or due to a negative feedback mechanism .…”

Section: Discussionmentioning

confidence: 99%

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The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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Summary A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant up‐regulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA‐1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as interleukin‐1β (IL‐1β), IL‐6 and IL‐18. The data obtained provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid‐induced analgesia through the modulation of neuroimmune interactions.

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Section: Discussionmentioning

confidence: 99%

“…IL‐18 also belongs to the IL‐1 superfamily . The pronociceptive actions of IL‐18 are under the control of its naturally occurring antagonist IL‐18BP, which can be produced constitutively or due to a negative feedback mechanism . After repeated intrathecal J113863 treatment, the spinal level of IL‐18 was decreased.…”

Section: Discussionmentioning

confidence: 99%

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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“…IL-18 is another pleiotropic pronociceptive cytokine that belongs to IL-1 superfamily (Pilat et al 2016; Samarani et al 2016). The pro-inflammatory effects of IL-18 are tightly controlled by its naturally occurring antagonist, called IL-18BP, which is produced due to a negative feedback mechanism (Dinarello and Fantuzzi 2003; Samarani et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…The pro-inflammatory effects of IL-18 are tightly controlled by its naturally occurring antagonist, called IL-18BP, which is produced due to a negative feedback mechanism (Dinarello and Fantuzzi 2003; Samarani et al 2016). Under physiological conditions, most IL-18 is bound with IL-18BP and inactivated.…”

Section: Discussionmentioning

confidence: 99%

The RS504393 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in Neuropathic Rats

Kwiatkowski

Piotrowska

Rojewska

et al. 2017

J Neuroimmune Pharmacol

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Increasing evidence has indicated that activated glial cells releasing nociceptive factors, such as interleukins and chemokines, are of key importance for neuropathic pain. Significant changes in the production of nociceptive factors are associated with the low effectiveness of opioids in neuropathic pain. Recently, it has been suggested that CCL2/CCR2 signaling is important for nociception. Here, we studied the time course changes in the mRNA/protein level of CD40/Iba-1, CCL2 and CCR2 in the spinal cord/dorsal root ganglia (DRG) in rats following chronic constriction injury (CCI) of the sciatic nerve. Moreover, we examined the influence of intrathecal preemptive and repeated (daily for 7 days) administration of RS504393, CCR2 antagonist, on pain-related behavior and the associated biochemical changes of some nociceptive factors as well as its influence on opioid effectiveness. We observed simultaneous upregulation of Iba-1, CCL2, CCR2 in the spinal cord on 7th day after CCI. Additionally, we demonstrated that repeated administration of RS504393 not only attenuated tactile/thermal hypersensitivity but also enhanced the analgesic properties of morphine and buprenorphine under neuropathy. Our results proof that repeated administration of RS504393 reduced the mRNA and/or protein levels of pronociceptive factors, such as IL-1beta, IL-18, IL-6 and inducible nitric oxide synthase (iNOS), and some of their receptors in the spinal cord and/or DRG. Furthermore, RS504393 elevated the spinal protein level of antinociceptive IL-1alpha and IL-18 binding protein. Our data provide new evidence that CCR2 is a promising target for diminishing neuropathic pain and enhancing the opioid analgesic effects.

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“…Similarly, levels are elevated in patients with chronic hepatitis and cirrhosis, and reduced after the infection is resolved either spontaneously (8) or after antiviral treatment (9). IL-18 levels are also elevated in HIV infection, an effect that is partially reversed by antiretroviral therapy (10,11). …”

Section: Introductionmentioning

confidence: 99%

Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections

et al. 2017

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Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines, including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. 1538 participants with active HIV and/or HCV infection in 3 ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with logIL-18 including HCV and HIV infection status and HIV-RNA, in each ancestry group and then meta-analyzed. Eleven highly correlated SNPs (r2=0.98-1) in the IL18-BCO2 region were significantly associated with logIL-18; Each T allele of rs80011693 confers a decrease of 0.06 log pg/mL of IL-18 after adjusting for covariates (rs80011693; rs111311302 β=-0.06, P-value=2.7×10-4). In conclusion, genetic variation in IL18 is associated with IL-18 production in response to HIV and HCV infection and may explain variability in the inflammatory outcomes of chronic viral infections.

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

Cited by 29 publications

References 133 publications

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

The RS504393 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in Neuropathic Rats

Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections

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