DISEASE PATTERNS AND TISSUE CYTOKINE PROFILES IN GIANT-CELL ARTERITIS

Objective. To determine whether clinical heterogeneity in patients wit h giant cell arteritis (GCA) is correlated with different patterns in the tissue-specific inflammatory response, Methods. Twenty-three patie nts with typical histomorphologic findings of GCA were grouped accordi ng to the presence or absence of jaw claudication and/or visual abnorm alities, fever, concomitant polymyalgia rheumatica (PMR), and histolog ic evidence of giant cell formation, The inflammatory response in temp oral artery biopsy specimens was characterized by semiquantification o f cytokine messenger RNA (mRNA) transcripts using reverse transcriptas e-polymerase chain reaction, followed by oligonucleotide hybridization with cytokine-specific probes. Clinical patterns were then correlated with profiles of tissue cytokines. Results. Inflammatory cytokines we re expressed in all temporal artery tissues, In situ synthesis of inte rleukin-2 (IL-2), interferon-gamma (IFN gamma), and IL-1 beta mRNA, bu t not of IL-10 and IL-12 mRNA, distinguished different patterns of inf lammation, and these patterns correlated with clinical manifestations of the disease, Patients with evidence of ischemic symptoms, indicated by jaw claudication and/or visual symptoms, typically expressed highe r concentrations of IFN gamma mRNA (P = 0.008) and IL-1 beta mRNA (P = 0.02), Presence of fever was correlated with lower copy numbers of IF N gamma (P = 0.02), Formation of giant cells in the granulomatous infi ltrates was associated with the local synthesis of IFN gamma mRNA (P = 0.003), Tissue from GCA patients with concomitant PMR contained highe r levels of IL-2 mRNA transcripts (P = 0.001). Conclusion. Variations in the clinical presentation of GCA were correlated with cytokine mRNA expression in the affected temporal arteries, Differences in the effe ctor functions of tissue-infiltrating T cells distinguished disease pa tterns in which either local ischemic symptoms or systemic involvement was dominant, or in which there was co-occurrence of PMR, Definition of different patterns of inflammation in GCA might, therefore, facilit ate the design of differentiated therapeutic approaches.