ࡱ> <>;q`bjbjqPqP80::HAvvv8LM       $hk(  ( (    ( 8   (     I?MvF p $0M a pa a ' 0W " y  ' ' ' & j' ' ' M( ( ( (  STUDY OF IL-23/IL-17 AXIS IN patients with Multiple Sclerosis UNtreated and treated with immunomodulator OR IMMUNOSUPRESSOR drugs PRELIMINARY RESULTS. Felipe von Glehn1,2, Carlos O. Brando1,2, Alessandro S. Farias1, Elaine C. Oliveira1, Ana Leda Longhini1, Juliana C. Sartorelli1, Fernando Pradella1, Rosemeire F. de Paula1, Juan Cabanillas1 Cassiana A. Horta2, Leonardo de Deus2, Alfredo Damasceno2, Alexander Schwarz3, Juergen Haas3, Brigitte Wildemann3, Benito P.Damasceno2, Leonilda M.B. Santos1 Laboratrio de Neuroimunologia do Instituto de Biologia (1), Ambulatrio de Esclerose Mltipla do Hospital das Clinicas da UNICAMP (2), UNICAMP, Campinas, SP, Brazil; Neurologische Klinik, Universidade de Heidelberg, Germany (3) Abstract: Multiple Sclerosis (MS) is a primary disease of the central nervous system, clinically characterized by relapses mediated by acute inflammatory lesions in the white matter, followed by a progressive phase, mediated by axonal and neuronal loss. The concept of MS as an autoimmune disease caused exclusively by Th 1 lymphocytes autoreactive to myelin components has been substituted by a more comprehensive hypothesis that takes into account the role of interleukin-17 (IL-17) producing CD4+ T cells (Th17) in interaction with T regulatory cells. However, the effect of IL-17 in patients with MS submitted to traditional treatment deserves more attention. Objective: Evaluate the modifications on the IL-23/IL-17 axis in patients with relapsing-remitting multiple sclerosis of less than 5 years duration non-treated and treated with immunomodulators or immunosuppressives drugs and compare with healthy controls. Material and Methods: The IL-17 was measured by ELISA in the serum and correspondent CSF from 20 patients. IL-17 was also quantified in the supernatants of cultured lymphocytes stimulated with PHA from 30 patients divided in three groups (10 untreated, 10 treated with Interferon-beta or Glatiramer acetate, 10 treated with corticosteroids or immunosuppressives). Healthy controls (n=20) were matched by age and gender. For proliferative responses comparing specific (myelin) and nonspecific (PHA) stimulation, mean incorporation of thymidine in DNA was measured in triplicate. The quantification of cytokines expression genes were evaluated using real time RT-PCR Results: Although the ELISA was very sensitive (less than 15 pg/ml), we could not detect directly IL-17 in serum and CSF of the patients. However, using the supernatant of nonstimulated cultured lymphocytes we have detected higher levels of IL-17 in untreated patients, which was statistically different from that found in the control group and treated with immunosuppressive drugs. Proliferative responses of lymphocytes stimulated with PHA and Myelin was significantly reduced in the treated group. The real time analysis also shows a modulation in the IL-23/IL-17 axis in the treated in relation to untreated individuals. Conclusion: Significant level of IL-17 was found in healthy individuals as well as in treatment naive MS patients, when lymphocytes were stimulated in culture by a nonspecific mitogen. Patients receiving immunomodulator or immunosuppressive drugs exhibit significantly reduced IL-17 levels, which was confirmed by real time PCR analysis, accompanied by a marked reduction of the proliferative response of T lymphocytes, reflecting the actions of these drugs. This result suggests that the traditional treatment of MS patients may also impact the Th17 lymphocyte subpopulation. Thus, the longitudinal quantification of IL-17 may be used as an inflammatory marker for monitoring the treatment of MS patients.     Financial support: FAPESP, CNPq and FAEPEX-UNICAMP  >@h{     - . 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