Tissue production of pro-inflammatory cytokines (IL-1β, TNFα and IL-6) correlates with the intensity of the systemic inflammatory response and with corticosteroid requirements in giant-cell arteritis

Objectives. To investigate proinflammatory cytokine expression in temporal arteries from patients with giant-cell arteritis (GCA) and to analyse its relationship with the intensity of the initial systemic inflammatory reaction and response to corticosteroid therapy. Methods. Quantification of interleukin-1b (IL-1b), tumor necrosis factor a (TNFa), and interleukin-6 (IL-6) mRNA by real-time quantitative PCR in temporal artery samples from 36 patients with biopsy-proven GCA and 11 controls. Immunohistochemical detection of IL-1b, TNFa, and IL-6 in temporal artery sections from 74 patients with GCA and 15 controls. Clinical and biochemical parameters of inflammation as well as the time (weeks) required to reach a maintenance prednisone dose <10 mg/day were recorded. Results. IL-1b (13.8 � 2.5 vs 5.4 � 1.3 relative units, P ¼ 0.012) and IL-6 transcripts (34 � 13.7 vs 7.8 � 4.5 relative units, P ¼ 0.034) were significantly more abundant in patients with a strong systemic inflammatory response compared with those with no inflammatory parameters. Immunohistochemical scores for IL-1b (2.7 � 0.3 vs 1.9 � 0.2, P ¼ 0.018), TNFa (3.2 � 0.2 vs 2.4 � 0.3, P ¼ 0.028) and IL-6 (3 � 0.2 vs 2.1 � 0.3, P ¼ 0.023) were also significantly higher in patients with strong systemic inflammatory reaction. A significant correlation was found between the amount of tissue TNFa mRNA and the time required to reach a maintenance dose of prednisone <10 mg/day (r ¼ 0.586, P ¼ 0.001). Conclusion. GCA patients with a strong systemic inflammatory response, who have been previously shown to be more resistant to corticosteroid therapy, have elevated tissue expression of proinflammatory cytokines IL-1b, TNFa and IL-6. High production of TNFa is associated with longer corticosteroid requirements.