The Primary and Memory Immune Response to Epstein–Barr Virus Infection In Vitro is Characterized by a Divergent Production of IL‐1β/IL‐6 and IL‐10

Abstract

Jabs WJ, Wagner HJ, Schlenke P, Kirchner H. The Primary and Memory Immune Response to EPSTEIN± BARR Virus Infection In Vitro is Characterized by a Divergent Production of IL-1b/IL-6 and IL-10. Scand J Immunol 2000;52:304±308 Reactivation of latent Epstein±Barr virus (EBV) infection is considered to exert substantial immunomodulating activities. Little is known about EBV's modulating activities on cytokine production upon primary, in contrast to reactivated, infection. Therefore, we investigated the cytokine production of latently infected EBV-positive (EBV-pos) adults upon in vitro EBV stimulation compared to nonimmune age-matched EBVnegative (EBV-neg) donors. Production of interleukin (IL)-1b and IL-6 was strongly decreased in peripheral blood mononuclear cell (PBMC) cultures of EBV-pos adults; in contrast, IL-10 and IL-1 receptor antagonist exhibited signi®cantly higher levels. As expected, interferon (IFN)-g production was almost exclusively observed in EBV-pos donors; it was accompanied by a signi®cantly higher IL-12 synthesis. Experiments employing T cell-depleted PBMC showed similar cytokine levels between EBV-pos and EBV-neg individuals suggesting that reactivation of EBV-speci®c memory T cells was responsible for the divergent cytokine pro®les. Production of viral IL-10 was excluded as a reason for higher IL-10 levels in EBV-pos individuals. In conclusion, our results do not appear to relate to any primary immunological differences between EBV-neg and EBV-pos adults, but show that the EBV-speci®c memory response to latent EBV infection is characterized by some anti-in¯ammatory effects. This might be of relevance upon reactivation of latent EBV infection in vivo and provides further evidence that EBV infection acts in an immunomodulating fashion.

Age-associated Epstein–Barr virus-specific T cell responses in seropositive healthy adults

“…Overall, our results are consistent with previous reports for individuals aged < 50 years, regarding the secretion of soluble IFN-γ, IL-6 and IL-10 in the presence of LCLs or lytic and latent-stage antigens (e.g. BZLF1, BMLF1, EBNA-1, EBNA-3C, LMP1, LMP2) [4,6,34,[40][41][42][43][44][58][59][60]. In contrast, the higher levels of TNF-α, IFN-γ and IL-6 found among individuals aged more than 50 years is a new observation related to EBV responses; these results suggest that individuals aged more than 50 years have an EBVcompetent immune response alongside low-grade inflammation that may emerge with age (e.g.…”

“…Jabs et al [58] have demonstrated that the IFN-γ and IL-10 levels produced by PBMCs depleted of T lymphocytes are decreased compared with whole PBMCs exposed to LCL supernatants, indicating the direct involvement of T lymphocytes in EBV responses. However, the presence of these cytokines in the culture supernatant cannot be attributed only to T lymphocytes, because other mononuclear cells such as monocytes may also be involved, as shown in the evaluation of the response to herpesviruses such as CMV [49].…”

Epstein-Barr virus: Is there any contribution to chronic hepatitis B and C?

“…It is considered to exert some immunomodulating activities. Reactivation of the EBV‐specific T cells leads to significant production of several cytokines, especially IFN‐γ, interleukin (IL)‐1, IL‐2 and IL‐10 (3). Additionally, the EBV BCRF1 product is a viral IL‐10 that shares high sequence homology with human IL‐10 and exerts the same activity.…”

Bell’s Palsy May Associate with Increased IL1R1: A Pilot Novel Gene and lncRNA Study

“…A possible explanation of Epstein-Barr virus mediated neural dysfunction is the activation of apoptotic pathways and intra-axonal degradation. For example, IL-1 and IL1R were found increased after EBV infection or even in nasopharyngeal carcinoma cell growth [31][32][33]. IL-1 signaling plays an important role in inflammation and early activation of host innate immune responses following virus infection [34].…”