T-CELL CYTOKINE PATTERN IN THE JOINTS OF PATIENTS WITH LYME ARTHRITISAND ITS REGULATION BY CYTOKINES AND ANTICYTOKINES

Objective. To investigate whether type 1 helper (Th1) or Th2 cytokines are found in the joints of patients with Lyme arthritis, and whether the cytokine pattern can be modulated by cytokines or anticytokines. M ethods. The cytokine pattern in the joints of 10 patients with Lyme ar thritis was investigated, Expression of interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), interleukin-4 (IL-4), and IL- 10 was measured by enzyme-linked immunosorbent assay (ELISA), after st imulation of synovial fluid mononuclear cells (SFMC) with Borrelia bur gdorferi (Bb) in the supernatant. Expression of cytokine messenger RNA and protein in synovial membrane (SM) and nonstimulated SFMC was stud ied using semiquantitative reverse transcriptase-polymerase chain reac tion and immunohistologic techniques, The effects of recombinant cytok ines or neutralizing anticytokine antibodies on cytokine production in Bb-stimulated SFMC were investigated by ELISA, Results. SFMC produced high amounts of IFN gamma and TNF alpha, but little or no IL-4, upon stimulation with Bb antigen, indicating a Th1-type cytokine pattern, I n SM, IFN gamma was detectable in all patients, while the other cytoki nes were less frequently found, Serial sections of SM, revealed that a ll cytokines were located in the same area, The Th1 response, especial ly the production of TNF alpha, could be down-regulated in vitro by bo th endogenous and exogenous IL-10, but not by IL-4 or anti-IL-12. Conc lusion. A Th1-type cytokine pattern was found in the joints of patient s with Lyme arthritis, This Th1 response could be down-regulated by IL -10, suggesting insufficient IL-10 production in vivo.