CHRONIC-FATIGUE-SYNDROME - IDENTIFICATION OF DISTINCT SUBGROUPS ON THE BASIS OF ALLERGY AND PSYCHOLOGIC VARIABLES

Background: We investigated a role for allergic inflammation and psych ologic parameters in the development of chronic fatigue syndrome (CFS) , Methods: The design was a comparison between subjects with CFS and a ge- and sex-matched control cohorts. Studies were performed on CFS sub jects (n =18) and control cohorts consisting of normal subjects (n = 1 1), allergic subjects (n = 14), and individuals with primary depressio n (n = 12), We quantified cytokines at baseline as cell-associated imm unoreactive peptides and as transcripts evaluated by means of semiquan titative RNA-based polymerase chain reactions. Psychologic evaluations included administration of the Diagnostic Interview Schedule, the Str uctured Clinical Interview, and the Symptom Checklist 90-Revised. Resu lts: Increases in tumor necrosis factor (TNF)-alpha were identified in individual subjects with CFS (50.1 +/- 14.4 pg TNF-alpha per 10(7) pe ripheral blood mononuclear cells [PBMCs]; mean +/- SEM) and allergic s ubjects (41.6 +/- 7.6) in comparison with normal subjects (13.1 +/- 8. 8) (P <.01 and P <.05, respectively), Similar trends were observed for interferon (IFN)-alpha in allergic subjects (3.0 +/- 1.7 pg/10(7) PBM Cs) and subjects with CFS (6.4 +/- 3.4) compared with normal subjects (1.9 +/- 1.4), A significant increase (P <.05) in TNF-alpha transcript s was demonstrated between subjects with CFS and depressed subjects. I n contrast to these proinflammatory cytokines, both subjects with CFS (2.6 +/- 1.8 pg/10(7) PBMCs) and allergic subjects (3.4 +/- 2.8) mere associated with a statistically significant (P <.01) decrease in IL-10 concentrations compared with normal subjects (60.2 +/- 18.2). As show n in other studies, most of our subjects with CFS were allergic (15 of 18) and therefore presumably demonstrated cytokine gene activation on that basis. The seasonal exacerbation of allergy was associated with a further increase in cellular IFN-alpha (from 2.1 +/- 1.2 to 14.2 +/- 4.5 pg/10(7) PBMCs; P <.05) but no further modulation of TNF-alpha or IL-10. Similarly, self-reported exacerbations of CFS were associated with a further increase in IFN-alpha (from 2.5 +/- 1.0 to 21.9 +/- 7.8 ; P <.05) and occurred at times of seasonal exposures to allergens. Th is Linkage does not permit making any definitive conclusions regarding a causative influence of either seasonal allergies or the increase in cellular IFN-alpha with the increase in CFS symptoms. The close assoc iation between atopy and CFS led us to speculate that CFS may arise fr om an abnormal psychologic response to the disordered expression of th ese proinflammatory and antiinflammatory cytokines. Psychologic variab les were predictive of immune status within the CFS sample (65.9% of t he variance in immune status; F (3,10) = 6.44, P <.05), Specifically, the absence of a personality disorder but greater endorsement of globa l psychiatric symptoms was predictive of immune activation. Conclusion s: Most of our subjects with CFS were allergic, and the CFS and allerg y cohorts were similar in terms of their immune status. However, the C FS subjects could be discriminated by the distinct psychologic profile s among subjects with and without immune activation. We propose that i n at lease a large subgroup of subjects with CFS who had allergies, th e concomitant influences of immune activation brought on by allergic i nflammation in an individual with the appropriate psychologic profile may interact to produce the symptoms of CFS, In a psychologically pred isposed individual, symptoms associated with allergic inflammation are recognized as illness.