Sulfasalazine aggravates experimental autoimmune encephalomyelitis and causes an increase in the number of autoreactive T cells.
Sulfasalazine (SASP; 5-(p-(2-pyridylsulfamoyl)phenylazo)salicyclic acid) has beneficial effects on certain inflammatory diseases and has been proposed for clinical trials in multiple sclerosis (MS). We have explored the effects of SASP on actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. SASP was given orally at three different doses from the day of immunization to day 40 post-immunization (p.i.). All doses led to a clinically more protracted disease, increased numbers of T cells infiltrating into the central nervous system (CNS) and to increased numbers of interferon-gamma-secreting cells (IFN-gamma-sc) in the CNS. The effects of SASP treatment on T cell-mediated autoimmunity against CNS myelin and peptides of myelin basic protein (MBP) were measured by IFN-gamma secretion and proliferation by lymph node mononuclear cells in response to these antigens. In SASP-treated rats, increased numbers of IFN-gamma-sc appeared in response to myelin antigens, while the proliferative responses were decreased. We suggest that monitoring cell-mediated immunity with the IFN-gamma-sc method may be relevant for the evaluation of new immunotherapeutic strategies in inflammatory demyelinating diseases. Furthermore, our results demand caution as to clinical trials with SASP in MS.
Department of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
J
J
Correale
T
T
Olsson
J
J
Björk
G
G
Smedegård
B
B
Höjeberg
H
H
Link
D000818:Animals; D001921:Brain / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D012460:Sulfasalazine / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D012460:Sulfasalazine; D007371:Interferon-gamma