CYTOKINE PRODUCTION IN A WHOLE-BLOOD ASSAY AFTER EPSTEIN-BARR-VIRUS INFECTION IN-VIVO

Epstein-Barr virus (EBV) has a marked tropism for cells of the immune system, and infection can result in profound immunomodulatory effects. In order to examine the role of cytokines during the acute phase of i nfectious mononucleosis, we studied the levels of different interleuki ns (ILs), interferons (IFNs), and the soluble IL-2 receptor (sIL-2R) i n serum samples of 20 patients. We found elevated levels of IL-2, IL-6 , sIL-2R, and IFN-gamma. Whereas the peak of IL-2 and IL-6 concentrati on occurred during the first week (P < 0.01), the largest amounts of s IL-2R were measured during the second week (P < 0.01). IFN-gamma level s were only enhanced during the first week In addition, we investigate d the ability to produce cytokines in response to mitogenic stimulatio n in a whole-blood assay of 11 patients compared with healthy blood do nors. In the whole-blood assay of patients compared with controls afte r stimulation with lipopolysaccharide, we measured more than 10-fold e levated levels of tumor necrosis factor alpha (P < 0.01), 3-fold eleva ted levels of IL-1 beta (P < 0.01), and about 2-fold increased amounts of IL-6 (P < 0.01). A significant enhancement in sIL-2R and IFN-gamma concentration was found in the assay after stimulation with phytohema gglutinin after 24 h of incubation (P < 0.01). Collectively, our data seem to indicate that monocytes are strongly activated during infectio us mononucleosis. Monocytes and monocyte-derived factors may play an i mportant role in the pathogenesis of infectious mono-nucleosis and, to gether with T lymphocytes, may be partly responsible for clinical symp toms.