Cytokine dysregulation in the post-Q-fever fatigue syndrome

The post-Q-fever fatigue syndrome (QFS) (inappropriate fatigue, myalgia andarthralgia, night sweats, changes in mood and sleep patterns) follows about20% of laboratory-proven, acute primary Q-fever cases. Cytokinedysregulation resulting from chronic immune stimulation and modulation bypersistence 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- term culture, from 18patients with active QFS, and 27 controls: six with resolving QFS, five whohad had acute primary Q-fever without subsequent QFS, eight healthy Q-fevervaccinees and eight healthy subjects without Q-fever antibody. Conditionedmedia (CM) from PBMC stimulated in short-term culture with Q-feverantigens, PHA or measles antigen (as an unrelated antigen) were assayed forIL-2, IL-4, IL-5, IL- 6, IL-10 and IFN gamma by AgEIA, and for IL-1 and TNFalpha/beta by bioassay. Aberrant cytokine release patterns were observedwith PBMC from QFS patients when stimulated with Q-fever antigens: anaccentuated release of IL-6 which was significantly [p = 0.01,non-parametric one- way analysis of variance (ANOVA)] in excess of mediansfor all four control groups. With IL-2, the number of responders in theactive QFS group was decreased relative to control groups (Fisher's exacttest, p = 0.01) whereas the number of IFN gamma responders was increased(Fisher's exact test, p = 0.0008). Significant correlations were observedbetween concentrations of IL-6 in CM, total symptom scores, and scores forother key symptoms.