Arterial wall production of cytokines in giant cell arteritis: results of a pilot study using human temporal artery cultures.
BACKGROUND
Giant cell arteritis (GCA) is a subacute periarteritis predominantly affecting segments of the external carotids of elderly patients. Vasculitic lesions in GCA samples might be characterized by in situ production of cytokines mRNA, indicative of macrophage and T-cell activation. However, whether the cytokine production of vessels with arteritis differs from that of vessels exposed to inflammatory conditions that originate peripheral to the vessel remains unknown.


METHODS
We investigated cytokine and soluble receptor cytokine production in blood samples and cultures of human temporal arteries from 22 consecutive patients (mean age 77 +/- 6 years) further investigated for possible diagnosis of GCA: 7 patients had GCA and 15 had neither GCA nor vasculitis but had other inflammatory, infectious, or malignant diseases (controls). The production of cytokines and soluble cytokine receptors in the supernatants of cultures of 3-mm segments of temporal artery specimens, before and after lipopolysaccharide (LPS) stimulation (10 ng/ml and 10 microg/ml) and in serum, was quantified using sandwich enzyme-linked immunosorbent assay (ELISA).


RESULTS
Cytokine production by temporal arteries increased significantly and in a dose-dependent manner (p <.01) after LPS stimulation in all patients studied, suggesting that the system is methodologically functional. Despite a large interindividual variation, we found similar differences in cytokine production before and after stimulation by 10 ng/ml and 10 microg/ml LPS between both groups: temporal arteries of GCA patients produced more interleukin (IL)-1beta (p <.05) and IFNgamma (nonsignificant) and less tumor necrosis factor (TNF)alpha (p <.05) and IL-6 (nonsignificant) than temporal arteries of controls. The levels of TNFalpha (p <.05) and IL-6 soluble receptor (p <.05) were significantly lower in GCA patients as compared with controls in blood samples, whereas levels of cytokines in temporal artery and in blood samples were not significantly correlated at the individual level in both groups.


CONCLUSIONS
The present pilot study, which requires further confirmation on a larger number of well-defined patients with GCA, suggests that a specific arterial cytokine production profile might exist in GCA (high IL-1beta +/- IFNgamma and low TNFalpha), addresses the question of the mechanisms by which IL-1beta and TNFalpha might be differentially regulated at the level of the arterial cell wall, and supports the view that cultures of the temporal artery might be an interesting tool for evaluating the role of cytokines in GCA pathogenesis.
Blain
Hubert
H
Department of Internal Medicine and Geriatrics, University Hospital, Montpellier, France.
Abdelmouttaleb
Idritia
I
Belmin
Joël
J
Blain
Arielle
A
Floquet
Jacques
J
Guéant
Jean-Louis
JL
Jeandel
Claude
C
D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D013700:Giant Cell Arteritis / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007375:Interleukin-1 / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D010865:Pilot Projects; D013699:Temporal Arteries / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma