CYTOKINE DYSREGULATION IN THE POST-Q-FEVER FATIGUE SYNDROME

The post-Q-fever fatigue syndrome (QFS) (inappropriate fatigue, myalgi a and arthralgia, night sweats, changes in mood and sleep patterns) fo llows about 20% of laboratory-proven, acute primary Q-fever cases. Cyt okine dysregulation resulting from chronic immune stimulation and modu lation by persistence of Coxiella burnetii cells or their antigens is hypothesized. We studied cytokine release patterns of peripheral blood mononuclear cells (PBMC) stimulated with various ligands in short-ter m culture, from 18 patients with active QFS, and 27 controls: six with resolving QFS, five who had had acute primary Q-fever without subsequ ent QFS, eight healthy Q-fever vaccinees and eight healthy subjects wi thout Q-fever antibody. Conditioned media (CM) from PBMC stimulated in short-term culture with Q-fever antigens, PHA or measles antigen (as an unrelated antigen) were assayed for IL-2, IL-4, IL-5, IL-6, IL-10 a nd IFN gamma by AgEIA, and for IL-l and TNF alpha/beta by bioassay. Ab errant cytokine release patterns were observed with PBMC from QFS pati ents when stimulated with Q-fever antigens: an accentuated release of IL-6 which was significantly [p = 0.01, non-parametric one-way analysi s of variance (ANOVA)] in excess of medians for all four control group s. With IL-2, the number of responders in the active QFS group was dec reased relative to control groups (Fisher's exact test, p = 0.01) wher eas the number of IFN gamma responders was increased (Fisher's exact t est, p = 0.0008). Significant correlations were observed between conce ntrations of IL-6 in CM, total symptom scores, and scores for other ke y symptoms.