title: Reduced Th2 cytokine production by sarcoidosis patients in clinical remission with chronic fatigue.
abstract: When the inflammatory phase of sarcoidosis has resolved, complaints of chronic fatigue frequently persist. Low-grade residual inflammatory activity may play a role in maintaining chronic fatigue. The aim of this study was to compare in vitro cytokine/chemokine production and plasma cytokine/chemokine levels between chronically fatigued and non-fatigued patients with sarcoidosis in clinical remission. Patients with sarcoidosis in clinical remission were assigned to a non-fatigued group (n=38) or a fatigued group (n=34) based on the standardized cut-off of the fatigue questionnaire Checklist Individual Strength. Cytokines/chemokines in plasma and in supernatants of whole blood cultures stimulated with either a T cell mitogen or lipopolysaccharide were quantified by multiplex analysis. Associations of cytokine/chemokine profiles with chronic fatigue were analyzed by multivariate analysis of variance and principal component analysis followed by logistic regression. Principal component analysis of T cell mitogen-induced cytokine/chemokine production identified three components that explained 76% of the variance in the cytokine/chemokine data. Logistic regression revealed that the 'Th2 cytokine'-component which mainly consists of interleukin (IL)-4, IL-5 and IL-10 was significantly and negatively associated with chronic fatigue. In addition, multivariate analysis revealed higher levels of LPS-induced IL-8 and lower levels of plasma monocyte chemoattractant protein (MCP)-1 in the fatigued group compared to the non-fatigued group. In chronically fatigued sarcoidosis patients in clinical remission, we found a cytokine/chemokine profile which is suggestive for a less competent Th2 counterbalancing capacity, that may contribute to the persistence of chronic fatigue.
authors.affiliation: Center of Interstitial Lung Diseases, Department of Pulmonology, St. Antonius Hospital Nieuwegein, Netherlands.
authors.forename: Ingrid H E
authors.initials: IH
authors.lastname: Korenromp
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
authors.forename: Jules M M
authors.initials: JM
authors.lastname: van den Bosch
authors.forename: Pieter
authors.initials: P
authors.lastname: Zanen
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
mesh_terms: D000328:Adult; D018925:Chemokines / Q000096:biosynthesis / Q000097:blood; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D016208:Databases, Factual; D005221:Fatigue / Q000097:blood / Q000150:complications / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D012507:Sarcoidosis / Q000097:blood / Q000150:complications / Q000276:immunology*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D018925:Chemokines; D016207:Cytokines