Interleukin 16 expression in relation to disease activity in rheumatoid arthritis.
OBJECTIVE
Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology characterized by an infiltration of CD4+ T lymphocytes within the rheumatoid synovium. Cytokines have been shown to play a modulatory role in the pathogenesis of RA. We analyzed the expression of a T cell derived cytokine. interleukin 16 (IL-16), in relation to disease activity to characterize its biologic function in RA.


METHODS
Secreted IL-16 was measured by enzyme immunoassay in sera and synovial fluids (SF) from 25 patients with RA in comparison to 20 control samples from patients with osteoarthritis (OA). IL-16 expression in peripheral blood mononuclear cells (PBMC) was characterized by flow cytometric analysis after intracellular cytokine staining for IL-16. In synovial tissue specimens, IL-16 mRNA expression was analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). In parallel, expression of IL-16 was localized in synovial tissues by in situ hybridization and immunohistochemistry. Results were analyzed in relation to disease activity.


RESULTS
IL-16 was detected at significantly higher levels in sera and SF of patients with RA in comparison to OA (p < 0.001). Flow cytometry of PBMC showed that a great proportion of both CD4+ and CD8+ T cells constitutively expressed the IL-16 protein. In synovial tissues, IL-16 mRNA levels were significantly elevated in comparison to OA controls (p < 0.001). In situ hybridization for IL-16 producing cells revealed a predominant accumulation of IL- 16 positive cells within the inflammatory infiltrates. A significant correlation between IL- 16 expression and local inflammatory activity could not be established (r = 0.27, p = 0.19) by microscopic analysis of the synovial cell infiltrate. In addition, no significant association was observed between serum, SF, and synovial tissue expression of IL-16 and clinical disease activity in RA.


CONCLUSIONS
These data suggest IL-16 might play a role in the pathogenesis of chronic inflammation in RA. The lack of significant correlation between IL-16 expression, clinical disease activity, and local inflammatory activity suggests a regulatory rather than a proinflammatory function for IL-16 in the pathogenesis of chronic synovial inflammation in RA.
Blaschke
S
S
Department of Nephrology and Rheumatology, University of Göttingen, Germany. sblasch@gwdg.de
Schulz
H
H
Schwarz
G
G
Blaschke
V
V
Müller
G A
GA
Reuss-Borst
M
M
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017403:In Situ Hybridization; D019410:Interleukin-16 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D000074402:Synovectomy; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000737:chemistry / Q000473:pathology
D017931:DNA Primers; D019410:Interleukin-16; D012333:RNA, Messenger