Antibodies to human IL-10 neutralize ebvIL-10-mediated cytokine suppression but have no effect on cmvIL-10 activity

Interleukin-10 is a pivotal determinant of virus clearance or persistence. Two human herpesviruses, Epstein–Barr virus (EBV) and human cytomegalovirus (HCMV) are unique among persistent viruses because they not only trigger production of host IL-10, but both viruses also encode homologs of IL-10 that are expressed during infection. Because anti-human IL-10 antibodies have diagnostic value and therapeutic potential for many chronic infections, cross-reactivity with ebvIL-10 and cmvIL-10 was evaluated in this study. Six of seven anti-hIL-10 antibodies tested recognized ebvIL-10 and neutralized its immunosuppressive activity. In contrast, cmvIL-10 was neither recognized nor neutralized by any anti-human IL-10 antibody. These findings demonstrate that IL-10-neutralizing treatments in HCMV- or EBV-infected patients may require consideration of the contribution of viral IL-10 to disease pathology.

Research highlights▶ Human IL-10-specific antibodies cross react with ebvIL-10 by Western blot and ELISA. ▶ cmvIL-10 is antigenically distinct from human IL-10 and ebvIL-10. ▶ Neutralizing antibodies block human IL-10 and ebvIL-10 function.