Latent Cytomegalovirus (CMV) Infection Exacerbates Severity of Dextran Sodium Sulfate (DSS) Colitis

CMV infection positively correlates with severity of inflammatory bowel disease (IBD). This may result from CMV triggering and/or exacerbating flares of IBD and/or reflect that IBD, or immunosuppressive drugs used in IBD, increases susceptibility to CMV infection. Thus, we sought to 1) Determine whether infection with CMV modulated gut inflammation in colitis‐prone mice and 2) Define if underlying CMV infection affected the colitis triggered by the colitogen DSS. CMV (1 x 10 5 PFU/ml/mouse) was administered i.p. to C57BL/6 mice (WT or IL‐10 −/− ). Some mice were later (28 d) placed on water containing 2.75% DSS. In accordance with previous studies, by 3 d, CMV administration resulted in an acute infection in which the virus was readily detected in numerous organs including the intestine and then, by 30 d, waned to a "latent" infection (PCR‐detectable in liver and salivary gland). Such CMV infection, in the acute or latent stage, did not induce colitis in WT mice nor alter severity of colitis in IL‐10 −/− mice. However, underlying CMV infection, in an acute or latent state, increased intestinal cytokine production (KC and IL‐6) and markedly potentiated the severity of colitis induced by DSS. DSS did not induce CMV "reactivation". Thus, in conclusion, underlying CMV infection, in an active or latent state, potentiates gut innate immunity and, consequently, may increase the tendency of CMV‐infected hosts to develop colitis.